266:32153221, 1991. endobj Second Messengers and Bell, R.M. BT S and transmitted securely. 0 g Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. U{7>O5HjQZ_= "\^QR)pxZm.DLXgE\sbg WQp1.0pxz-/(kvek0iKp(&i 6=x18mY^+Bo:sAs \=z18=ORo\pN'66ox+k {{x6S.VfzC>9,vek wn$atB}q^/c?t:?uxEEM:M$I89We^ Rfs5vscZ$V1zdtd>^_{ [7nnYgr\3[cyvD d{pnn>^_|jN$a\5nQpqZQ:*:"18p|gcZSp pU\n+~~9GnhZ<17J JJa`$a!~wRP_\p'O:CbiY|[7nj77z( pGQI'Q'D>;irkai.c{;R A AFF1g\z4x}-fsun;\j. Briefly, MCF-7 cells (3,000 cells/well) were plated in 96-well plates. (Computation, and Decision Making)Tj ET 10 0 0 10 60 485 Tm 3-phosphoinositide-dependent protein kinase-1 regulates proliferation and survival of cancer cells with an activated mitogen-activated protein kinase pathway, Sustained MAP kinase activation is required for the expression of cyclin D1, p21Cip1 and a subset of AP-1 proteins in CCL39 cells. 2017 May 16;8(20):33694-33703. doi: 10.18632/oncotarget.16624. Relative quantification of lipids was provided, and data were reported as the peak area ratios of the analytes to the internal standard. PIP2 second messenger system is the most important lipid second messengers that mediate cell signaling transduction. 4C). These data suggest that AKR1B10 stimulates breast cancer cell growth and proliferation through activation of DAG-mediated PKC/ERK signaling pathway. 8:138153, 1993. More impressively, AKR1B10 promoted clonogenic growth of MCF-7 cells, a feature of cancer cells. An aliquot (10 l) of the cell suspension was used for protein quantitation, and the remainder was mixed vigorously with 20 volumes of chloroform/ methanol (2:1, v/v). DAG activates important oncogenic signaling molecule PKC, and IP3 provokes ER-mediated calcium signaling, further activating PKC. Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. This site needs JavaScript to work properly. AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-B signaling pathway. Lipid samples and standards were visualized by coloration in staining solution (0.12 M NaCl, 20% methanol, and 300 mg/liter Coomassie Blue). Proc. DAG and IP 3 are second messengers that can act independently or in unison. 10 0 0 10 50 447 Tm ET 3A, AKR1B10 expression in MCF-7 cells enhanced the level of phosphorylated PKC (Thr505), PKC (Ser744/748) and PKC/II (Thr638/641). /T1_1 1 Tf The second messenger pathway which concerns the intracellular action of Ca2+ ions is involved in a variety of actions that include the collaboration with DAG for the activation of PKC and the calcium-modulated protein (calmodulin or Cam) kinase pathway. More importantly, membrane phospholipids are a major group of lipid second messengers, mediating cellular signaling pathways of cancer cell growth and proliferation [1]. Second Messengers Bioenergetics Investigating Photosynthesis Biological Molecules ATP Carbohydrates Condensation Reaction DNA and RNA DNA replication Denaturation Enzymes Factors Affecting Enzyme Activity Fatty Acids Hydrolysis Reaction Inorganic Ions Lipids Measuring enzyme-controlled reactions Monomers Monomers and Polymers Monosaccharides MOG treatment elevated DAG levels up to 4-fold in unstimulated platelets. (Subject Collection)Tj After incubation on ice for 10 min, debris was removed at 21,000 xg for 10 min, and the supernatant was washed with 0.2 volume of distilled water. More importantly, AKR1B10 is a mediator of long chain fatty acid synthesis. /T1_2 1 Tf 10 0 0 10 238.36987 554 Tm Q: Name and describe the role of hormones secreted by ovaries, testes and placenta. As shown in Figure 6D, the PKC/ERK signaling pathway was activated by AKR1B10 in tumors. . 2018 Oct; 57(10): 13001310. Casey, P., Solski, P.A., Der, C.J. It is noteworthy to note that AKR1B10 can promote cell survival through protection from reactive carbonyl lesions [13,17,37]. *, p<0.05 and **, p<0.01 when compared to vector control. S The levels of second messengers are exquisitely. Science 238:17261728, 1987. This study addressed the gap of AKR1B10 knowledge and dissected the signaling pathways, through which AKR1B10 stimulates the growth and proliferation of breast cancer cells. These results are in consistence with clinical settings that AKR1B10 expression in breast cancer correlates with tumor size and worse disease-free survival [31]. -14.28398 0 Td (Second Messengers)Tj Wu Y, Qi Y, Bai Y, Zhang H, Zhu W, Zhou S, Zhang Y. and Buss, J.E. Following thrombin stimulation, (/sup 32/P)phosphatidic acid formation likely reflects the initial agonist-receptor interaction; therefore, these results suggest that phospholipase C activity is enhanced in platelets of SHR and that the hypersensitivity of phospholipase C in SHR may play a role in the overall alteration of cell calcium handling and, hence, in the platelet responses of SHR. CrossRef Values were normalized for protein contents (CPM/mg of protein). Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U. and Nishizuka, Y. J. Biol. (Signals and Receptors)Tj Ctrl: control. 2022 Springer Nature Switzerland AG. 2021 Aug 21;11(1):163. doi: 10.1186/s13578-021-00677-3. Before . These keywords were added by machine and not by the authors. Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. Acrobat Distiller 11.0 (Windows) In many cases the response of the cell membrane is the production of small rapidly diffusible "second messenger" substances inside the cell. The phosphorylation-activated ERK1/2 translocates into the nucleus where it phosphorylates and activates MSK, p90RSK and transcription factors (e.g., c-Myc, Elk-1 and Ets-1) to stimulate cell growth and proliferation [10]. Li J, Guo Y, Duan L, Hu X, Zhang X, Hu J, Huang L, He R, Hu Z, Luo W, Tan T, Huang R, Liao D, Zhu YS, Luo DX. 0 0 m Role of the Polyol Pathway in Locomotor Recovery and Wallerian Degeneration after Spinal Cord Contusion Injury. BT 148 0 obj 0 g A: We can say that Hormones can be described as the chemical secreted by specialized cells of endocrine. (Evren U. Azeloglu and Ravi Iyengar)Tj 10 0 0 10 60 379 Tm Q 10 0 0 10 318 485 Tm The p-ERK1/2, p-p90RSK and p-MSK levels and Cyclin D1 expression were increased by AKR1B10 in the cells, and the increased p-p90RSK, p-MSK and Cyclin D1 levels were eradicated by MEK inhibitor, U0126 (10 M). The https:// ensures that you are connecting to the BT Am. Oppositely, silencing of AKR1B10 in BT-20 cells led to decrease in total lipids, PIP2 and IP3 (Fig. BT PubMedGoogle Scholar, Wayne State University, Detroit, Michigan, USA, Vanderbilt University, Nashville, Tennessee, USA, 1997 Springer Science+Business Media New York, Quest, A.F., Ghosh, S., Xie, W.Q., Bell, R.M. ET Long chain fatty acids are precursors of lipids and are the main components of biomembrane phospholipids. 1A). This effect could not be explained by decreased intracellular levels of diC/sub 10/, or by saturation of DAG kinase with endogenous DAGs. 10 0 0 10 318 508.99997 Tm 10 0 0 10 60 335 Tm 8:32353243, 1988. ET Introduction Diacylglycerol (DAG) is a lipid signal messenger which is an essential second messenger in mammalian cells. PubMed For example, a 20-second exposure to thrombin, 0.3 U/ml, induced the formation of 1.6 times more (/sup 32/P)phosphatidic acid in SHR than in WKY. Quality control (QC) samples were prepared by pooling the aliquots of study samples and were used to monitor instrument stability. (Signaling by the TGF)Tj These results define an oncogenic role of AKR1B10 in growth and progression of breast cancer and clarify the mechanisms of action. ET ET AKR1B10 is an oncoprotein that promotes growth and progression of breast cancer. PMC legacy view These compounds were tested in human platelets. 10 0 0 10 318 358.99997 Tm Aldo-keto reductase 1B10 (AKR1B10), also referred as aldose reductase-like-1 (ARL-1) [11], is a monomeric enzyme with strong catalytic activity to , -unsaturated carbonyl compounds [12-14] and protects the host cells from carbonyl lesions [15-17]. The As shown in Fig. Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 2 pp 297303Cite as, Part of the Advances in Experimental Medicine and Biology book series (AEMB,volume 400). H1nga_`y\@,vm\X,lx 7)"+v\x )(o$"TP)P{ Ah(%vy oQ y ?NA|gJr:7[| c~9dYx}mZ`[ )hn~S* izAht:1g)E.%}{r|:Wp &=8& It was observed that cyclooxygenase products were responsible for collagen-induced guinea pig platelet aggregation. *, p<0.05 and **, p<0.01 when compared to AKR1B10 Control cells. Disclaimer, National Library of Medicine 10 0 0 10 318 437 Tm HHS Vulnerability Disclosure, Help (al. On the other hand, RHC 80267 was a powerful inhibitor of aggregation and ADP release induced by all three of these potent aggregating agents. Second messengers. endobj Acad. 10 0 0 10 60 311 Tm 3C). Oncotarget. (Nicholas Rhind and Paul Russell)Tj All were found to be effective in stimulating glucose transport. to target molecules in the cytosol and/or nucleus. IP 3, DAG, and Ca 2+ are second messengers in the phosphoinositol pathway. Thus we further observed the effect of AKR1B10 on proliferation and tumorigenesis of breast cancer cells. DC and JJ worked in all aspects of the project and revised the manuscript. <> The minimal sequence required for PDBu binding was elucidated by deletion analysis. uuid:79068d31-c36f-4e54-9b1e-32efcd71848f /T1_2 1 Tf ET <> Biologically, AKR1B10 promotes fatty acid/lipid synthesis. <>/ExtGState<>/Font<>/ProcSet[/PDF/Text]/Properties<>>>/Rotate 0/Type/Page>> Phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC) are two major mediators of cellular lipid messengers. Down-regulation of aldo-keto reductase AKR1B10 gene expression by a phorbol ester via the ERK/c-Jun signaling pathway. <>/Filter/FlateDecode/Height 300/Length 34147/Name/X/Subtype/Image/Type/XObject/Width 1200>>stream ( Superfamily)Tj Chem 261:93419347, 1986. The site is secure. ET -8.11398 0 Td 3Drug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute, and Departments of Oncologic Sciences and Chemistry, University of South Florida, 12902 Magnolia Drive, Tampa, Florida 33612-9416, United States. This may explain the functional role of AKR1B10 in breast cancer growth and progression. endobj Chem. Leach, K.L., Ruff, V.A., Wright, T.M., Pessin, M.S. However, little is known of the molecular mechanisms of action. Proc., Fed. 10 0 0 10 308 495 Tm 4A Author contributions: CH and ZC were involved in experimental studies and data analysis and CH also participated in discussion, wrote the draft and prepared Figures. In studies of the properties of DAG kinase with pure DAGs in mixed detergent micelles, they found that the enzyme phosphorylated arachidonoyl-DAG more readily than diC/sub 10/. 50 96 m AII (5 x 10/sup -7/M) causes only a transient contractile response, while PE (10/sup -5/M) causes a sustained tonic contraction. (Alexandra C. Newton, Martin D. Bootman and John)Tj Our data showed that ectopic expression of AKR1B10 in breast cancer cells . G-protein coupled receptors (GPCRs) and tyrosine kinase receptors (TKRs) are important upstream activators of lipid second messengers. Careers, The publisher's final edited version of this article is available at, GUID:E2FCDCBA-1036-4140-99CD-716FC3170795, AKR1B10, breast cancer, lipid second messengers, phosphatidylinositol bisphosphate, diacylglycerol, PKC/ERK cascade, Cancer Metabolism: A Modeling Perspective, Signal transduction through lipid second messengers. We further assessed the effect of AKR1B10 on clonogenic growth of MCF-7 cells in three-dimensional (3D) culture in growth factor-reduced extracellular matrix that mimics in vivo environment of mammary epithelial cells. Department of Molecular Cancer Biology, Duke University Medical Center, Durham, NC, 27710, USA, Andrew F.G. Quest,Sujoy Ghosh,Wen Qin Xie&Robert M. Bell, You can also search for this author in (B) Raf/MER/ERK activation by AKR1B10, showing p-Raf, p-MEK and p-ERK1/2 levels in the MCF-7 with ectopic expression of AKR1B10 and BT-20 cells with silencing of AKR1B10. While DAG stays inside the membrane, IP3is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum. ET Exp. (A) PKC activation by AKR1B10, showing p-PKC (Thr505), p-PKC (Ser744/748) and p-PKC/II (Thr638/641) levels in the MCF-7 with ectopic expression of AKR1B10 and BT-20 cells with silencing of AKR1B10. /T1_2 1 Tf 0 1.00001 TD The pathway begins with the binding of extracellular primary messengers such as epinephrine, acetylcholine, and hormones AGT, GnRH, GHRH, oxytocin, and TRH, to their respective receptors. 2022-12-11T18:18:39-08:00 The results showed that ectopic expression of AKR1B10 promoted clonogenic growth in both 2D and 3D cultures and tumorigenesis in nude mice, but silencing of AKR1B10 suppressed growth and proliferation of breast cancer cells. 10 0 0 10 50 423 Tm 2B). 2) by activation of enzyme in cell membrane. BT /T1_2 1 Tf (Peter Devreotes and Alan Rick Horwitz)Tj P30 CA076292/CA/NCI NIH HHS/United States, P30 DK020579/DK/NIDDK NIH HHS/United States, NCI CPTC Antibody Characterization Program. To verify that the PDGF effect on PA/sub 10/ formation in intact cells was due to reduced phosphorylation of diC/sub 10/ by DAG kinase, cells were treated with PDGF and/or diC/sub 10/, freeze-thawed, and then incubated with Mg(/sup 32/P)ATP. RHC 80267, a diacylglycerol lipase inhibitor, and indomethacin, a cyclooxygenase inhibitor, were used. and transmitted securely. Only the lipid species with CV < 15% in QC sample were reported. The glycerol is linked with the fatty acid chain through ester linkages. As shown in Fig. To confirm the cancer-promoting role of AKR1B10, we further evaluated its effects on growth of tumor xenografts in vivo. Accessibility The .gov means its official. A pellet of 17-estradiol (0.72mg/pellet) was implanted beneath the neck skin. /T1_1 1 Tf <> Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips. At endpoint, we collected tumors and evaluated the phospho-PKC isoforms and phospho-ERK. In brief, lipids were extracted from 5106 cells using a modified Bligh-Dyer method in the presence of an internal standard DG15:0-15:0 (0.5 g per sample). [251 0 R 252 0 R 253 0 R 254 0 R] FOIA DAG second messengers: molecular switches and growth control Adv Exp Med Biol. 266:1833018338, 1991. S Lipid fractions were re-suspended into 50% methanol solution, and radioactivity were measured by scintillation counter (Beckman Instruments). BT In breast cancer cells, the activated ERK signaling by AKR1B10 enhanced cell growth and proliferation through phosphorylation activation of p90RSK and MSK and expression of cyclin D1, and this was proven by pharmacological inhibition of ERK1/2 activity using MEK1/2 inhibitors U0126 and PD98059. /T1_1 1 Tf (C) Acinar formation and growth of MCF-7 cells in the Matrigel-based 3D culture. Currie E, Schulze A, Zechner R, Walther TC, Farese RV Jr. Cellular fatty acid metabolism and cancer, Metabolic pathways promoting cancer cell survival and growth, Membrane lipids: where they are and how they behave, Phosphoinositide lipid second messengers: new paradigms for transepithelial signal transduction, Pflugers Archiv : European journal of physiology, Protein kinase C (PKC) family in cancer progression, Protein kinase C and other diacylglycerol effectors in cancer, MAPK signal pathways in the regulation of cell proliferation in mammalian cells, Identification and characterization of a novel human aldose reductase-like gene, Substrate specificity and catalytic efficiency of aldo-keto reductases with phospholipid aldehydes, Aldo-keto reductase family 1 B10 protein detoxifies dietary and lipid-derived alpha, beta-unsaturated carbonyls at physiological levels, Biochemical and biophysical research communications, Human aldo-keto reductases 1B1 and 1B10: A comparative study on their enzyme activity toward electrophilic carbonyl compounds. The DAG formed was in a pool where it did not activate protein kinase C. Thrombin-stimulation of MOG-treated platelets resulted in DAG levels 10-fold higher than control platelets. 562 568 l (Neal M. Alto and Kim Orth)Tj /T1_1 1 Tf T* *, p<0.05 and **, p<0.01 when compared to vector control. This section summarizes the attributes of some of the principal second messengers.Figure 8.7Neuronal second messengers. In this study, the authors have compared the effects of concanavalin A, EGF, IGF-I and sodium orthovanadate to insulin on PA/DG synthesis, C-kinase activity and glucose transport. In the center, binding of ligands to a GPCR (receptor) activates phospholipase C (PLC; the effector), to generate two second messengers, DAG and IP 3, which activate protein kinase C (PKC; the target) and release calcium from intracellular stores, respectively. (A) Proliferation of MCF-7 and BT-20 cells measured by Alamar blue assays (left) and cell counting assays (right). 562 96 l Zu X, Yan R, Robbins S, Krishack PA, Liao DF, Cao D. Reduced 293T cell susceptibility to acrolein due to aldose reductase-like-1 protein expression, Toxicological sciences : an official journal of the Society of Toxicology, Oxidative Stress and Carbonyl Lesions in Ulcerative Colitis and Associated Colorectal Cancer, Oxidative medicine and cellular longevity, Development of a 32P-postlabelling method for the detection of 1,N2-propanodeoxyguanosine adducts of crotonaldehyde in vivo, Microbially produced acetaldehyde from ethanol may increase the risk of colon cancer via folate deficiency, International journal of cancer Journal international du cancer, Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10, Proceedings of the National Academy of Sciences of the United States of America, Aldo-keto reductases from the AKR1B subfamily: retinoid specificity and control of cellular retinoic acid levels, AKR1B10 induces cell resistance to daunorubicin and idarubicin by reducing C13 ketonic group. government site. BT Platelets were labeled with (/sup 14/C)arachidonic acid to facilitate sensitive determination of small changes in platelet phospholipids during platelet aggregation. 0 0 1 rg application/pdf 4China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, 541001, Guangxi, China. 10 0 0 10 308 529 Tm luciferase substrate D-luciferin at 100 mg/kg in PBS and anesthetized by isoflurane. Medium was added with 1/10 (v/v) Alamar blue and changed regularly every 24hr. (Douglas R. Green and Fabien Llambi)Tj Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. Martin HJ, Breyer-Pfaff U, Wsol V, Venz S, Block S, Maser E. Purification and characterization of akr1b10 from human liver: role in carbonyl reduction of xenobiotics, Drug metabolism and disposition: the biological fate of chemicals, Aldo-keto reductase family 1 B10 affects fatty acid synthesis by regulating the stability of acetyl-CoA carboxylase-alpha in breast cancer cells, Increased lipogenesis in cancer cells: new players, novel targets, Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis, Overexpression and oncogenic function of aldo-keto reductase family 1B10 (AKR1B10) in pancreatic carcinoma, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. Fukumoto S, Yamauchi N, Moriguchi H Together these data suggest that in breast cancer cells, AKR1B10 promotes lipogenesis and increases the cellular levels of important lipid second messengers, PIP2, IP3 and DAG. USA 83:11841188, 1986. (Signal Transduction)Tj the two second messengers produced by the activity of enzyme Phospholipase C Therefore, it seemed that endogenous DAGs, derived from PI, might be better substrates for DAG kinase than is diC/sub 10/. /T1_0 1 Tf Mice were placed onto a warm stage inside a light-tight camera box with continuous exposure to isoflurane. Europe PMC is an archive of life sciences journal literature. (B) Levels of various subspecies of DAG in MCF-7 (upper), BT-20 (lower left) and HCT-8 (lower right) cells. <>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/Type/Page>> These lipid second messengers activate PKC and thus the PKC-mediated ERK signaling cascade, promoting growth and proliferation of breast cancer cells (Fig. ET Neurosci. endobj ERK1/2 also induces cyclin D1 expression through an AP-1 mediated mechanism, stimulating G1/S progression and cell proliferation [10,40]. They examined effects of concanavalin A and EGF on C-kinase activity and found that both agonists, like insulin, increase C-kinase activity in cytosolic and/or membrane fractions. With PDGF treatment, the radioactivity in endogenous PA increased fourfold, whereas the radioactivity in PA/sub, Thrombin-induced aggregation and serotonin release were markedly enhanced in platelets from spontaneously hypertensive rats (SHR) when compared with those from normotensive Wistar-Kyoto rats (WKY). In particular, we quantitatively measured total cellular DAG and all 16 subspecies using LC-MS through the core facility in Washington University at St Louis, and the results strengthened the quality and accuracy of our data. Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas, Clinical cancer research : an official journal of the American Association for Cancer Research, AKR1B10 overexpression in breast cancer: association with tumor size, lymph node metastasis and patient survival and its potential as a novel serum marker, Epidermal growth factor induces tumour marker AKR1B10 expression through activator protein-1 signalling in hepatocellular carcinoma cells, AKR1B10 promotes breast cancer metastasis through integrin alpha5/delta-catenin mediated FAK/Src/Rac1 signaling pathway. -0.549 0 Td (Synaptic Signaling in Learning and Memory)Tj endobj and Raben, D.M. These data suggest that the ERK1/2 signaling activated by AKR1B10 promotes cell growth and proliferation through the targets p90RSK, MSK and cyclin D1 in the breast cancer cells. PKC isoforms are master kinases of the important signaling cascade, Raf/MEK/ERK, regulating a variety of cellular events, such as cell survival and proliferation. Before House, C. and Kemp, B.E. Tumor volume was measured using in vivo bioluminescent imaging with an IVIS VR imaging system (Xenogen, CA) and also measured by Vernier caliper. Together these data suggest that AKR1B10 promotes clonogenic growth and proliferation of breast cancer cells. BT ET In breast cancer cells, AKR1B10 promoted the clonogenic growth and proliferation of breast cancer cells in two-dimension (2D) and three-dimension (3D) cultures and tumor growth in immunodeficient female nude mice through activation of the PKC/ERK pathway. Unable to display preview. In the present investigation it is shown that collagen, thrombin, The authors investigated the properties of Diacylglycerol (DAG) Kinase in 3T3 cells. Figure 6.. AKR1B10 promotes tumor growth in female nude mice. BT We used the LC-Mass Core facility of Washington University at St Louis to quantitatively measure total DAG and 16 subspecies in cells with targeted expression or silencing of AKR1B10 (Supplemental Figure S1). Cells (4000/well) were seeded. /T1_2 1 Tf 4A, ectopic expression of AKR1B10 in MCF-7 increased the cell growth and proliferation compared to the empty vector control, whereas silencing of AKR1B10 in BT-20 cells decreased the cell proliferation. Download full-text PDF Read full-text. An official website of the United States government. National Library of Medicine Sci. Qualitative analyses by liquid chromatography-mass spectrum (LC-MS) revealed that AKR1B10 regulated the cellular levels of total DAG and majority of subspecies. monitored as changes in (/sup 32/P)phosphatidic acid, was significantly higher in SHR than in WKY. Yan R, Zu X, Ma J, Liu Z, Adeyanju M, Cao D. Aldo-keto reductase family 1 B10 gene silencing results in growth inhibition of colorectal cancer cells: Implication for cancer intervention, Separation of phosphatidylinositols and other phospholipids by two-step one-dimensional thin-layer chromatography. 6/21/2016by Yonas Teshome 4 R and R' are saturated or unsaturated hydrocarbon chains. /T1_2 1 Tf 10 0 0 10 60 437 Tm /T1_2 1 Tf Second Messengers Often the extracellular message is a chemical (hormone or neurotransmitter), which binds to its receptor on the cell membrane, which in turn triggers events in the membrane. (A) Inhibition of MCF-7 cell proliferation by MEK inhibitors, PD98059 and U0126 at 10 M or 20 M. endobj In Press. 10/ and PI/sub 10/ was consistently decreased. BT These results suggest that the inability of AII to maintain tension, unlike PE, is due to its inability to produce DAG continuously and activate protein kinase C. Insulin, concanavalin A, EGF, IFG-I and vanadate activate de novo phosphatidic acid and diacylglycerol synthesis, C-kinase, and glucose transport in BC3H-1 myocytes, Mechanism for release of arachidonic acid during guinea pig platelet aggregation: a role for the diacylglycerol lipase inhibitor RHC 80267, Substrate selectivity of diacylglycerol kinase in PDGF-stimulated 3T3 cells, Hypersensitivity of phospholipase C in platelets of spontaneously hypertensive rats, Evidence for a requirement of agonist-induced diacylglycerol production during tonic contraction of rat aorta. endobj Natl. (Signaling Networks: Information Flow,)Tj (Subversion of Cell Signaling by Pathogens)Tj 0 1 TD AKR1B10 promotes biosynthesis of long chain fatty acids by stabilizing ACCA [26]. Therefore, we examined phosphorylation activation of PKC isoforms. endobj These messengers differ in the mechanism by which they are produced and removed, as well as their downstream targets and effects (Figure 8.7A). **, p<0.01 when compared to AKR1B10 Control cells. /T1_1 1 Tf Figure 3.. AKR1B10 activates PKC/ERK signaling pathway in breast cancer cells. Quest, A.F.G., Bardes, E.S.G. DiC/sub 10/ was added to the cell medium before harvesting. 0 g These data suggest that AKR1B10 promotes breast cancer growth in vivo by activating the PKC/ERK signaling pathway, being an oncogenic protein in breast cancer growth and progression. Since phosphoinositides are involved in calcium-mediated platelet responses, the metabolism of these lipids was investigated in SHR and WKY by using /sup 32/P-labeled quiescent platelets. (B) Tumor volumes by in vivo bioluminescence at photon/second. 10 0 0 10 308 378.99997 Tm 193 0 obj ET about navigating our updated article layout. /Im0 Do 10 0 0 10 308 471 Tm INTRODUCTION Second messengers are molecules that relay signals from receptors on the cell surface to target molecules inside the cell. However, little is known of the molecular mechanisms of action. 8 0 0 8 260.42407 754 Tm Revealing potential lipid biomarkers in clear cell renal cell carcinoma using targeted quantitative lipidomics. (Second Messengers)Tj Google Scholar. Epub 2014 Nov 22. The new PMC design is here! A number of DAG analogs were tested as substrates and inhibitors of partially purified pig brain DGK. Moreover, the extent of the difference between SHR and WKY was independent of the extracellular calcium concentration. ET Google Scholar. AKR1B10 is upregulated in human breast cancer and correlates with tumor size and lymph node metastasis [31], but the underlying molecular mechanisms are unclear. /T1_3 1 Tf The high proliferation of cancer cells depends on lipid synthesis to meet both the needs of biomembrane synthesis in cell division and function as signal molecules, stimulating cell growth and proliferation [5]. It functions as a second messenger that facilitates the protein kinase C (PKC) enzyme's movement from the . In the breast cancer cells, AKR1B10 promotes lipogenesis and increases cellular lipid second messengers PIP2, IP3 and DAG, which activates the PKC/ERK signaling cascade. (Signaling Pathways that Regulate Cell Division)Tj /T1_1 1 Tf Proc. ET Analytical data of DAG subspecies demonstrated that targeted expression of AKR1B10 markedly increased the levels of majority of 16 DAG subspecies, but AKR1B10 silencing led to decrease of DAG subspecies (Fig. Biol. 10 0 0 10 50 471 Tm /T1_2 1 Tf 10 0 0 10 50 389 Tm 10 0 0 10 50 495 Tm /T1_1 1 Tf However, little is known of the molecular mechanisms of action. /T1_1 1 Tf Would you like email updates of new search results? After packaging in 293T cells, AKR1B10 and empty pCDH lentiviral particles were introduced into cells with standard procedures. Ahmed, S., Kozma, R., Lee, J., Monfries, C., Harden, N. and Louis, L. Biochem. BT Although repetitive observations were not conducted in these breast cancer cells with targeted expression or silencing of AKR1B10, we believe that the carbonyl detoxification mechanism of AKR1B10 may also contribute to the cell growth and proliferation. 0 0 1 rg Y axis is in log10. DAG and IP 3 are second messengers that can act independently or in unison. A scrambled siRNA with random RNA sequences was used as a control. /T1_2 1 Tf Lu Z, Cox-Hipkin MA, Windsor WT, Boyapati A. -19.28497 0 Td PMC The development of specific inhibitors of DAG kinase and DAG lipase, in conjunction with mass quantification of DAG levels as used here, will providemore further insights into the regulation of DAG second messengers.less, The authors have reported that insulin stimulates de novo synthesis of phosphatidic acid (PA) which is metabolized directly to diacylglycerol (DG) in BS3H-1 myocytes; this is accompanied by increases in C-kinase activity in membrane and cytosolic extracts. Tel: (314) 747-0677. eCollection 2021. 2006 Jun;27(6):317-23. doi: 10.1016/j.tips.2006.04.003. (D. Scott)Tj Accessibility ET Bethesda, MD 20894, Web Policies 8600 Rockville Pike 189 0 obj The organic phase was collected and dried by speed vacuum. endstream (In Press), Quest, A.F.G., Bardes, E.S.G. The mechanism of enhanced phosphorylation of DAG was studied with dicaprylin (diC/sub 10/) as a probe. HHS Vulnerability Disclosure, Help *, p<0.05 and **, p<0.01 when compared to vector control. J. 0 0 m eCollection 2022. Figure 5.. ERK signaling and target genes, Figure 5.. ERK signaling and target genes that are involved in cell proliferation enhanced by, Figure 6.. AKR1B10 promotes tumor growth in. 1Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine. Our data showed that ectopic expression of AKR1B10 in breast cancer cells MCF-7 promoted lipogenesis and enhanced levels of lipid second messengers, including phosphatidylinositol bisphosphate (PIP2), diacylglycerol (DAG) and inositol triphosphate (IP3). It was also discovered that cyclooxygenase products were responsible for further stimulation (a positive feed-back) of phospholipase C activity, while diacylglycerol provided a negative feed-back control over receptor-stimulated phospholipase C activity and inhibited ADP release. Huang C, Verhulst S, Shen Y, Bu Y, Cao Y, He Y, Wang Y, Huang D, Cai C, Rao K, Liao DF, Jin J, Cao D. Oncotarget. The p90RSK, MSK and cyclin D1 functions as downstream targets of the ERK1/2 in this process. ET /T1_0 1 Tf BT We thus assessed the effect of targeted AKR1B10 expression on growth and proliferation of breast cancer cells. DAG has a great role in biochemical signaling. Each nude mouse was implanted with a 1.7 mg of 17-estradiol pellet (Innovative Research of America, CA) to support MCF-7 proliferation. Search terms: Advanced search options. T* 10 0 0 10 318 311 Tm Plating efficiency was calculated as: Colony number/seeded cell number. This result was confirmed by both Alamar blue (Fig. After being air-dried, plates were developed in hexane/diethyl ether/acetic acid (70/30/1, v/v) to separate neutral lipids, such as DAG, or in chloroform/methanol/acetic acid (65/25/10, v/v) to separate phospholipids, such as PIP2 and IP3. Interestingly, this study found that aldo-keto reductase 1B10 is a novel regulator of intracellular lipid messengers. Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. Left panel: Quantitative analysis of band intensity. 122 0 obj Download full-text PDF. (B) Plating efficiency of MCF-7 cells in cell culture dishes. Mol. PIP2 is a precursor of the important lipid second messenger diacylglycerol (DAG). Clipboard, Search History, and several other advanced features are temporarily unavailable. /sup 32/P-labelling studies showed that AII caused an initial increase of PA synthesis equal to PE, however, AII failed to sustain this increase at, Attenuation of diacylglycerol second messengers. (Signaling in Muscle Contraction)Tj /T1_2 1 Tf Grant support: This work was supported in part by National Natural Science Foundation of China (81472465 and 81772842) and Natural Science Foundation of Guangxi (2015GXNSFEA139003). Therefore, lipid second messengers are important cellular signal molecules that regulate cell growth, proliferation and survival. Lipids were dissolved in 50 l of chloroform/methanol (2:1, v/v). 10 0 0 10 50 321 Tm Ganong, B.R., Loomis, C.R., Hannun, Y.A. 2016 Jul 12;7(28):43779-43791. doi: 10.18632/oncotarget.9672. 245 0 obj (B) Plating efficiency of MCF-7 cells in cell culture dishes. Qualitative analyses by liquid chromatography-mass spectrum (LC-MS) revealed that AKR1B10 regulated the cellular levels of total DAG and majority of subspecies. Lipogenesis is increased in tumors and contributes to various aspects of tumorigenesis and progression, such as cell proliferation, differentiation and invasion [1,4]. 194 0 obj J. Biol. %PDF-1.4 % 130 0 obj As shown in Fig. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis, Journal of receptor and signal transduction research. Earl Wilbur Sutherland Jr . 1994 Sep;267(3 Pt 1):C659-78. Activated ERK1/2 phosphorylates several substrates, including p90RSK and MSK. ZOOLOGY 2. CAS Acetate incorporation into lipid species, including phosphatidylinositol-4,5-bisphosphate (PIP2), inositol-1,4,5- trisphosphate (IP3) and diacylglycerol (DAG), was analyzed by thin layer chromatography (TLC). PubMed PKC is an important oncogenic kinase that activates ERK1/2 signaling to promote cancer growth and progression [8,9]. BT Lipid extracts and appropriate lipid standards (Sigma, MO) were spotted on silica gel (60; Sigma, MO). The selectivity of DAG kinase may play a key role in the formation of arachidonoyl species of PI. Metabotropic signaling with G-protein coupling. IS, internal standard. This pathway may be involved in stimulating glucose transport and other metabolic processes. BT **, p<0.01 when compared to the vector control or PD98059/U0126-treated cells. As a carbonyl reductase, AKR1B10 also works as an efficient retinal reduction enzyme to convert retinals to retinols, thus mediating homeostasis of retinoid acid and cell differentiation [22,23]. BT The results showed that targeted AKR1B10 expression in MCF-7 cells increased total cellular DAG levels, but oppositely, silencing of AKR1B10 led to decrease of DAG in both BT-20 and HCT-8 cells (Fig. In brief, lipids were extracted from 510 6 cells using a modified Bligh-Dyer method in the presence of an internal standard DG15:0-15:0 (0.5 g per sample). A cysteine-rich region homologous to Cysl is also found in the protooncoprotein Raf-1 kinase. They are a component of cell signaling pathways. (B) Raf/MER/ERK activation by AKR1B10, showing p-Raf, p-MEK and p-ERK1/2 levels in the MCF-7 with ectopic expression of AKR1B10 and BT-20 cells with silencing of AKR1B10. (A) Proliferation of MCF-7 and BT-20 cells measured by Alamar blue assays (left) and cell counting assays (right). 0 0 1 rg Activation of protein kinase C with TPA prior to and during AII exposure converted the normally transient contraction to a more sustained, tonic pattern. BT uuid:b03733e8-1dd1-11b2-0a00-aa00a8a7ebff In breast cancer, AKR1B10 is upregulated in ductal carcinoma in situ (DCIS) and invasive, metastatic and recurrent tumors and correlates with tumor size, lymph node metastasis, and disease-related death. 10 0 0 10 308 447 Tm Acad. 2A). 4B). Careers. (Cold Spring Harb Perspect Biol\240)Tj Natl. ET (C) ERK inhibition by a broad PKC inhibitor, Go6893 (10M), showing decreased p-ERK1/2 level by Go6893 in the MCF-7 cells with AKR1B10 expression. Hannun, Y. and Bell, R.M. 5. Bookshelf Their findings raise the possibility that activation of receptors having associated tyrosine kinase activity may provoke some cellular responses through de novo PA/GD synthesis and C-kinase activation. Analogs were tested in human platelets Tj Chem 261:93419347, 1986 Tf Mice placed... Tj endobj and Raben, D.M lipase inhibitor, and indomethacin, a diacylglycerol lipase,.: 13001310 of targeted AKR1B10 expression on growth and metastasis decrease in total lipids, and. 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