摘要
В настоящее время общепринятой считается мутационная теория канцерогенеза, согласно которой в основе злокачественной трансформации лежит изменение генома клетки. Сигнальный каскад PI3K/Akt/mTOR является важным регулятором клеточного роста и метаболизма, а его патологическая активация обнаружена при различных онкологических заболеваниях. В данном обзоре рассмотрены изменения в PI3K сигнальном каскаде при различных онкопатологиях и обсуждается возможность их практического применения в диагностике и терапии.参考
Abid M.R., Guo S., Minami T. et al. Vascular endothelial growth factor activates PI3K/Akt/forkhead signaling in endothelial cells // Arterioscler Thromb Vasc Biol. - 2004. - Vol. 24. - P. 294-300.
Altiok S., Batt D., Altiok N. et al. Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells // J. Biol. Chem. -1999. - Vol. 274. - P. 32274-32278.
Bagrodia S., Smeal T, Abraham R.T. Mechanisms of intrinsic and acquired resistance to kinase-targeted therapies // Pigment. Cell Melanoma Res. - 2012. - Vol. 25. - P. 819-831.
Bai H., Li H., Li W. et al. The PI3K/AKT/mTOR pathway is a potential predictor of distinct invasive and migratory capacities in human ovarian cancer cell lines // oncotar-get. - 2015. - Vol. 6. - P. 25520-25532.
Banerjee S., Kaye S.B. New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential // Clin. Cancer Res. - 2013. - Vol. 19. - P. 961-968.
Cai J., Xu L., Tang H. et al. The role of the PTEN/PI3K/ Akt pathway on prognosis in epithelial ovarian cancer: a meta-analysis // Oncologist. - 2014. - Vol. 19. - P. 528-535.
Campbell I.G., Russell S.E., Choong D.YH. et al. Mutation of the PIK3CA gene in ovarian and breast cancer // Cancer Res. - 2004. - Vol. 64. - P. 7678-7681.
Campbell R.A., Bhat-Nakshatri P., Patel N.M. et al. Phos-phatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance // J. Biol. Chem. -2001. - Vol. 276. - P. 9817-9824.
Carden C.P., Stewart A., Thavasu P. et al. The association of PI3 kinase signaling and chemoresistance in advanced ovarian cancer // Mol. Cancer Ther. - 2012. - Vol. 11. - P. 1609-1617.
Cecconi S., Ciccarelli C., Barberi M. et al. Granulosa cell-oocyte interactions // Eur. J. Obstet. Gynecol. Reprod. Biol. - 2004. - Vol. 115. Suppl. - P. S19-22.
Cecconi S., Mauro A., Cellini V. et al. The role of Akt signalling in the mammalian ovary // Int. J. Dev. Biol. - 2012. - Vol. 56. - P. 809-817.
Chandarlapaty S., Sawai A., Scaltriti M. et al. AKT Inhibition Relieves Feedback Suppression of Receptor Tyrosine Kinase Expression and Activity //Cancer Cell. - 2011. - Vol. 19. - P. 58-71.
Chang Y-S., Hsu H.-T., Ko Y-C. et al. Combined mutational analysis of RAS, BRAF, PIK3CA, and TP53 genes in Taiwanese patients with oral squamous cell carcinoma // Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. - 2014. - Vol. 118. - P. 110-116.
Cheaib B., Auguste A., Leary A. The PI3K/Akt/mTOR pathway in ovarian cancer: therapeutic opportunities and challenges // Chin. J. Cancer. - 2015. - Vol. 34. - P. 4-16.
Cheung L.W.T., Hennessy B.T., Li J. et al. High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability // Cancer Discov. - 2011. - Vol. 1. - P. 170-185.
Cizkova M., Vacher S., Meseure D. et al. PIK3R1 underexpression is an independent prognostic marker in breast cancer // BMC Cancer. - 2013. - Vol. 13. - P. 545.
Coomans de Brach ne A., Demoulin J.-B. FOXO transcription factors in cancer development and therapy // Cell Mol. Life Sci. - 2016. - Vol. 73. - P. 1159-1172.
Cross M.J., Dixelius J., Matsumoto T. et al. VEGF-receptor signal transduction // Trends Biochem Sci. - 2003. - Vol. 28. - P. 488-494.
Datta S.R., Dudek H., Tao X. et al. Akt phosphorylation of BAD couples survival signals to the Cell-intrinsic death machinery // Cell. - 1997. - Vol. 91. - P. 231-241.
Dufour M., Dormond-Meuwly A., Pythoud C. et al. Reactivation of AKT signaling following treatment of cancer cells with PI3K inhibitors attenuates their antitumor effects // Biochem Biophys. Res. Commun. - 2013. - Vol. 438. - P. 32-37.
Ellis M.J., Lin L., Crowder R. et al. Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer // Breast Cancer Res. Treat. - 2010. - Vol. 119. - P. 379-390.
Engelman J.A. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. //Nat. Rev. Cancer. - 2009. - Vol. 9. - P. 550-562.
Engelman J.A., Luo J., Cantley L.C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism // Nat. Rev. Genet. - 2006. - Vol. 7. - P. 606-619.
Faes S., Dormond O. PI3K and AKT: Unfaithful Partners in Cancer // Int. J. Mol. Sci. - 2015. -Vol. 16. - P. 21138-21152.
Fang X., Yu S., Eder A. et al. Regulation of BAD phosphorylation at serine 112 by the Ras-mitogen-activated protein kinase pathway // Oncogene. - 1999. - Vol. 18. - P. 6635-6640.
Fernando R.I., Wimalasena J. Estradiol abrogates apop-tosis in breast cancer cells through inactivation of BAD: Ras-dependent nongenomic pathways requiring signaling through ERK and Akt // Mol. Biol. Cell. - 2004. - Vol. 15. - P. 3266-3284.
Ferrara N., Gerber H.-P., LeCouter J. The biology of VEGF and its receptors // Nat. Med. - 2003. - Vol. 9. - P. 669-676.
Fruman D.A., Meyers R.E., Cantley L.C. Phosphoinositide kinases // Annu. Rev. Biochem. -1998. - Vol. 67. - P. 481-507.
Furet P., Guagnano V., Fairhurst R.A. et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation // Bioorg. Med. Chem. Lett. - 2013. - Vol. 23. - P. 3741-3748.
Gonzalez-Angulo A.M., Chen H., Karuturi M.S. et al. Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast Cancer. // Cancer. - 2013. - Vol. 119. - P. 7-15.
Greenhough A., Patsos H.A., Williams A.C. et al. The can-nabinoid A9-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells // Int. J. Cancer. - 2007. - Vol. 121. - P. 2172-2180.
Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation // Cell. - 2011. - Vol. 144. - P. 646-674.
Hayes M.P., Wang H., Espinal-Witter R. et al. PIK3CA and PTEN mutations in uterine endometrioid carcinoma and complex atypical hyperplasia // Clin. Cancer Res. - 2006. - Vol. 12. - P. 5932-5935.
He Y, Van't Veer L.J., Mikolajewska-Hanclich I. et al. PIK-3CA mutations predict local recurrences in rectal cancer patients // Clin. Cancer Res. - 2009. - Vol. 15. - P. 6956-6962.
Hu L., Hofmann J., Lu Y et al. Inhibition of phosphati-dylinositol 3'-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models // Cancer Res. - 2002. - Vol. 62. - P. 1087-1092.
Huang C.-H., Mandelker D., Schmidt-Kittler 0. et al. The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations // Science. - 2007. - Vol. 318. - P. 1744-1748.
Huang J., Zhang L., Greshock J. et al. Frequent genetic abnormalities of the PI3K/AKT pathway in primary ovarian cancer predict patient outcome // Genes. Chromosomes. Cancer. - 2011. - Vol. 50. - P. 606-618.
Irie H.Y, Pearline R. V, Grueneberg D. et al. Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition // J. Cell Biol. - 2005. - Vol. 171. - P. 1023-1034.
Isakoff S.J., Engelman J.A., Irie H.Y et al. Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells // Cancer Res. - 2005. - Vol. 65. - P. 10992-11000.
Janku F., Tsimberidou A.M., Garrido-Laguna I. et al. PIK-3CA mutations in patients with advanced cancers treated with PI3K/AKT/mT0R axis inhibitors // Mol. Cancer Ther. - 2011. -Vol. 10. - P. 558-565.
Jiang B.H., Jiang G., Zheng J.Z. et al. Phosphatidylinosi-tol 3-kinase signaling controls levels of hypoxia-inducible factor 1 // Cell Growth Differ. - 2001. - Vol. 12. - P. 363-369.
Junttila T.T., Akita R.W., Parsons K. et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastu-zumab and is effectively inhibited by the PI3K inhibitor GDC-0941 // Cancer Cell. - 2009. - Vol. 15. - P. 429-440.
Kaur J., Sanyal S.N. PI3-kinase/Wnt association mediates C0X-2/PGE2 pathway to inhibit apoptosis in early stages of colon carcinogenesis: chemoprevention by diclofenac // Tumor Biol. -2010. - Vol. 31.- P. 623-631.
Krasilnikov M.A. Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation // Biochemistry (Mosc). - 2000. - Vol. 65. - P. 59-67.
Kristensen T.B., Knutsson M.L.T., Wehland M. et al. Anti-vascular endothelial growth factor therapy in breast cancer // Int. J. Mol. Sci. - 2014. - Vol. 15. - P. 2302423041.
Kuo K.-T, Mao T.-L., Jones S. et al. Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma // Am. J. Pathol. - 2009. - Vol. 174. - P. 1597-1601.
Kushlinskii N.E., Gershtein E.S. Role of vascular endothelial growth factor during breast cancer // Bull. Exp. Biol. Med. - 2002. - Vol. 133. - P. 521-528.
Lai K., Killingsworth M.C., Lee C.S. Gene of the month: PIK3CA // J. Clin. Pathol. - 2015. - Vol. 68. - P. 253257.
Levine D.A., Bogomolniy F., Yee C.J. et al. Frequent mutation of the PIK3CA gene in ovarian and breast cancers // Clin. Cancer Res. - 2005. - Vol. 11. - P. 2875-2878.
Liao X., Lochhead P., Nishihara R. et al. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival // N. Engl. J. Med. - 2012. - Vol. 367. - P. 1596-1606.
Liu P., Cheng H., Roberts T.M. et al. Targeting the phosphoinositide 3-kinase pathway in cancer // Nat. Rev. Drug. Discov. - 2009. - Vol. 8. - P. 627-644.
Liu S., Knapp S., Ahmed A.A. The structural basis of PI3K cancer mutations: from mechanism to therapy // Cancer Res. - 2014. - Vol. 74. - P. 641-646.
Liu Y, Sun S.-Y, Owonikoko T.K. et al. Rapamycin induces Bad phosphorylation in association with its resistance to human lung cancer cells // Mol. Cancer Ther. - 2012. - Vol. 11. - P. 45-56.
Lux M.P., Fasching P.A., Schrauder M.G. et al. The PI3K Pathway: Background and Treatment Approaches // Breast Care. - 2016. - Vol. 11. - P. 398-404.
Mao C., Yang Z.Y, Hu X.F. et al. PIK3CA exon 20 mutations as a potential biomarker for resistance to anti-EG-FR monoclonal antibodies in KRAS wild-type metastatic colorectal cancer: a systematic review and meta-analysis // Ann. Oncol. - 2012. - Vol. 23. - P. 1518-1525.
Matkar S., Sharma P., Gao S. et al. An Epigenetic Pathway Regulates Sensitivity of Breast Cancer Cells to HER2 Inhibition via FOXO/c-Myc Axis //Cancer Cell. - 2015. - Vol. 28. - P. 472-485.
Miled N., Yan Y, Hon W.-C. et al. Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit //Science. - 2007. - Vol. 317. - P. 239-242.
Murugan A.K., Hong N.T., Fukui Y et al. Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas // Int. J. Oncol. - 2008. - Vol. 32. - P. 101-111.
Di Nicolantonio F., Arena S., Tabernero J. et al. Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus // J. Clin. Invest. - 2010. - Vol. 120. - P. 2858-2866.
O Farrell F., Rusten T.E., Stenmark H. Phosphoinositide 3-kinases as accelerators and brakes of autophagy // FEBS J. - 2013. - Vol. 280. - P. 6322-6337.
Obata K., Morland S.J., Watson R.H. et al. Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors // Cancer Res. - 1998. - Vol. 58. - P. 2095-2097.
Paplomata E., O'Regan R. The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers // Ther Adv. Med. Oncol. - 2014. - Vol. 6. - P. 154-166.
Philp A.J., Campbell I.G., Leet C. et al. The phos-phatidylinositol 3'-kinase p85alpha gene is an oncogene in human ovarian and colon tumors // Cancer Res. - 2001. - Vol. 61. - P. 7426-7429.
Reagan-Shaw S. RNA Interference-Mediated Depletion of Phosphoinositide 3-Kinase Activates Forkhead Box Class O Transcription Factors and Induces Cell Cycle Arrest and Apoptosis in Breast Carcinoma Cells // Cancer Res. - 2006. - Vol. 66. - P. 1062-1069.
Robey R.B., Hay N. Is Akt the ‘Warburg kinase'?-Akt-en-ergy metabolism interactions and oncogenesis // Semin Cancer Biol. - 2009. - Vol. 19. - P. 25-31.
Saal L.H., Holm K., Maurer M. et al. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma // Cancer Res. - 2005. - Vol. 65. - P. 2554-2559.
Samuels Y, Velculescu V.E. Oncogenic mutations of PIK3CA in human cancers // Cell Cycle. -2004. - Vol. 3. - P. 1221-1224.
Samuels Y, Wang Z., Bardelli A. et al. High frequency of mutations of the PIK3CA gene in human cancers // Science. - 2004. - Vol. 304. - P. 554.
Scheijen B., Ngo H.T., Kang H., et al. FLT3 receptors with internal tandem duplications promote cell viability and proliferation by signaling through Foxo proteins. // Oncogene. -2004.-Vol. 23- P.3338-49.
Scherbakov A.M., Sorokin D. V, Tatarskiy V. V, et al. The phenomenon of acquired resistance to metformin in breast cancer cells: The interaction of growth pathways and estrogen receptor signaling. //IUBMB Life. -2016.-Vol. 68- P. 281-92.
Serra V., Scaltriti M., Prudkin L., et al. PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. // Oncogene. -2011.-Vol. 30- P.2547-57.
Smit L., Berns K., Spence K., et al. An integrated genomic approach identifies that the PI3K/AKT/FOXO pathway is involved in breast cancer tumor initiation. //Oncotarget. -2016.-Vol. 7- P.2596-610.
Song G., Ouyang G., Bao S. The activation of Akt/PKB signaling pathway and cell survival. //J Cell Mol Med. -2005.-Vol. 9- P.59-71.
Stein R.C. Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment. //Endocr Relat Cancer. -2001.-Vol. 8- P.237-48.
Taniguchi C.M., Winnay J., Kondo T, et al. The phosphoinositide 3-kinase regulatory subunit p85alpha can exert tumor suppressor properties through negative regulation of growth factor signaling. //Cancer Res. -2010.-Vol. 70- P.5305-15.
Tian W.-Y, Chen W.-C., Li R., et al. Markers CD40, VEGF, AKT, PI3K, and S100 correlate with tumor stage in gastric cancer. //Onkologie. -2013.-Vol. 36- P.26-31.
Velho S., Moutinho C., Cirnes L., et al. BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: primary or secondary genetic events in colorectal carcinogenesis? //BMC Cancer. -2008.-Vol. 8- P.255.
Volinia S., Hiles I., Ormondroyd E., et al. Molecular cloning, cDNA sequence, and chromosomal localization of the human phosphatidylinositol 3-kinase p110 alpha (PIK3CA) gene. //Genomics. -1994.-Vol. 24- P.472-7.
Wang L., Zhang Q., Zhang J., et al. PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib. //BMC Cancer. -2011.-Vol. 11- P.248.
Whitehall V.L.J., Rickman C., Bond C.E., et al. Oncogenic PIK3CA mutations in colorectal cancers and polyps. //Int J Cancer. -2012.-Vol. 131- P.813-20.
Whitman M., Kaplan D.R., Schaffhausen B., et al. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. //Nature. -1985.-Vol. 315- P.239-42.
Williams R.L., Walker E.H., Perisic O., et al. Structural insights into phosphoinositide 3-kinase catalysis and signalling. //Nature. -1999.-Vol. 402- P.313-20.
Wu G., Xing M., Mambo E., et al. Somatic mutation and gain of copy number of PIK3CA in human breast cancer. //Breast Cancer Res. -2005.-Vol. 7- P.R609-16.
Young N.R., Liu J., Pierce C., et al. Molecular phenotype predicts sensitivity of squamous cell carcinoma of the head and neck to epidermal growth factor receptor inhibition. //Mol Oncol. -2013.-Vol. 7- P.359-68.
Yu F. Involvement of post-transcriptional regulation of FOXO1 by HuR in 5-FU-induced apoptosis in breast cancer cells. //Oncol Lett. -2013.
Yue W., Wang X., Wang Y [The Relationship between the PI3K/Akt/mTOR Signal Transduction Pathway and Nonsmall Cell Lung Cancer.]. //Zhongguo Fei Ai Za Zhi. -2009.-Vol. 12- P.312-5.
Zhao L., Vogt P.K. Class I PI3K in oncogenic cellular transformation. //Oncogene. -2008.-Vol. 27- P.5486-96.
Zhong H., Chiles K., Feldser D., et al. Modulation of hy-poxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/ FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. //Cancer Res. -2000.-Vol. 60- P.1541-5.
Zhou X.D., Chen H.X., Guan R.N., et al. Protein kinase B phosphorylation correlates with vascular endothelial growth factor A and microvessel density in gastric adenocarcinoma. //J Int Med Res. -2012.-Vol. 40- P.2124-34.
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