Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2014

Open Access 01-12-2014 | Review

The impact of microRNA-mediated PI3K/AKT signaling on epithelial-mesenchymal transition and cancer stemness in endometrial cancer

Authors: Peixin Dong, Yosuke Konno, Hidemichi Watari, Masayoshi Hosaka, Masayuki Noguchi, Noriaki Sakuragi

Published in: Journal of Translational Medicine | Issue 1/2014

Login to get access

Abstract

Activation of the PI3K/AKT pathway, a common mechanism in all subtypes of endometrial cancers (endometrioid and non-endometrioid tumors), has important roles in contributing to epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) features. MicroRNAs (miRNAs) are small non-coding RNA molecules that concurrently affect multiple target genes, and regulate a wide range of genes involved in modulating EMT and CSC properties. Here we overview the recent advances revealing the impact of miRNAs on EMT and CSC phenotypes in tumors including endometrial cancer via regulating PI3K/AKT pathway. MiRNAs are crucial mediators of EMT and CSC through targeting PTEN-PI3K-AKT-mTOR axis. In endometrial cancer cells, miRNAs can activate or attenuate EMT and CSC by targeting PTEN and other EMT-associated genes, such as Twist1, ZEB1 and BMI-1. More detailed studies of miRNAs will deepen our understanding of the molecular basis underlying PI3K/AKT-induced endometrial cancer initiation and progression. Targeting key signaling components of PI3K/AKT pathway by restoring or inhibiting miRNA function holds promise as a potential therapeutic approach to suppress EMT and CSC in endometrial cancer.
Appendix
Available only for authorised users
Literature
1.
Siegel R, Ma J, Zou Z, Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 2014, 64: 9-29.PubMed
2.
Jin F, Devesa SS, Chow WH, Zheng W, Ji BT, Fraumeni JF, Gao YT: Cancer incidence trends in urban shanghai, 1972–1994: an update. Int J Cancer. 1999, 83: 435-440.PubMed
3.
4.
Bokhman JV: Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983, 15: 10-17.PubMed
5.
Singh P, Smith CL, Cheetham G, Dodd TJ, Davy ML: Serous carcinoma of the uterus-determination of HER-2/neu status using immunohistochemistry, chromogenic in situ hybridization, and quantitative polymerase chain reaction techniques: its significance and clinical correlation. Int J Gynecol Cancer. 2008, 18: 1344-1351.PubMed
6.
Alvarez T, Miller E, Duska L, Oliva E: Molecular profile of grade 3 endometrioid endometrial carcinoma: is it a type I or type II endometrial carcinoma?. Am J Surg Pathol. 2012, 36: 753-761.PubMed
7.
Mhawech-Fauceglia P, Wang D, Kesterson J, Syriac S, Clark K, Frederick PJ, Lele S, Liu S: Gene expression profiles in stage I uterine serous carcinoma in comparison to grade 3 and grade 1 stage I endometrioid adenocarcinoma. PLoS One. 2011, 6: e18066-PubMedCentralPubMed
8.
Moore KN, Fader AN: Uterine papillary serous carcinoma. Clin Obstet Gynecol. 2011, 54: 278-291.PubMed
9.
Slomovitz BM, Coleman RL: The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res. 2012, 18: 5856-5864.PubMed
10.
Sarmadi S, Izadi-Mood N, Sotoudeh K, Tavangar SM: Altered PTEN expression; a diagnostic marker for differentiating normal, hyperplastic and neoplastic endometrium. Diagn Pathol. 2009, 4: 41-PubMedCentralPubMed
11.
Rudd ML, Price JC, Fogoros S, Godwin AK, Sgroi DC, Merino MJ, Bell DW: A unique spectrum of somatic PIK3CA (p110alpha) mutations within primary endometrial carcinomas. Clin Cancer Res. 2011, 17: 1331-1340.PubMedCentralPubMed
12.
Lacey JV, Mutter GL, Ronnett BM, Ioffe OB, Duggan MA, Rush BB, Glass AG, Richesson DA, Chatterjee N, Langholz B, Sherman ME: PTEN expression in endometrial biopsies as a marker of progression to endometrial carcinoma. Cancer Res. 2008, 68: 6014-6020.PubMedCentralPubMed
13.
Matias-Guiu X, Prat J: Molecular pathology of endometrial carcinoma. Histopathology. 2013, 62: 111-123.PubMed
14.
Acharya S, Hensley ML, Montag AC, Fleming GF: Rare uterine cancers. Lancet Oncol. 2005, 6: 961-971.PubMed
15.
Zannoni GF, Scambia G, Gallo D: The dualistic model of endometrial cancer: the challenge of classifying grade 3 endometrioid carcinoma. Gynecol Oncol. 2012, 127: 262-263.PubMed
16.
Yeramian A, Moreno-Bueno G, Dolcet X, Catasus L, Abal M, Colas E, Reventos J, Palacios J, Prat J, Matias-Guiu X: Endometrial carcinoma: molecular alterations involved in tumor development and progression. Oncogene. 2013, 32: 403-413.PubMed
17.
Wild PJ, Ikenberg K, Fuchs TJ, Rechsteiner M, Georgiev S, Fankhauser N, Noske A, Roessle M, Caduff R, Dellas A, Fink D, Moch H, Krek W, Frew IJ: p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans. EMBO Mol Med. 2012, 4: 808-824.PubMedCentralPubMed
18.
Nout RA, Bosse T, Creutzberg CL, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, van Eijk R, Ter Haar NT, Smit VT: Improved risk assessment of endometrial cancer by combined analysis of MSI, PI3K–AKT, Wnt/β-catenin and P53 pathway activation. Gynecol Oncol. 2012, 126: 466-473.PubMed
19.
Kuhn E, Wu RC, Guan B, Wu G, Zhang J, Wang Y, Song L, Yuan X, Wei L, Roden RB, Kuo KT, Nakayama K, Clarke B, Shaw P, Olvera N, Kurman RJ, Levine DA, Wang TL, Shih IM: Identification of molecular pathway aberrations in uterine serous carcinoma by genome-wide analyses. J Natl Cancer Inst. 2012, 104: 1503-1513.PubMedCentralPubMed
20.
Dong P, Kaneuchi M, Konno Y, Watari H, Sudo S, Sakuragi N: Emerging therapeutic biomarkers in endometrial cancer. Biomed Res Int. 2013, 2013: 130362-PubMedCentralPubMed
21.
Chakrabarti R, Hwang J, Andres Blanco M, Wei Y, Lukačišin M, Romano RA, Smalley K, Liu S, Yang Q, Ibrahim T, Mercatali L, Amadori D, Haffty BG, Sinha S, Kang Y: Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. Nat Cell Biol. 2012, 14: 1212-1222.PubMedCentralPubMed
22.
Larue L, Bellacosa A: Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3′ kinase/AKT pathways. Oncogene. 2005, 24: 7443-7454.PubMed
23.
Chang L, Graham PH, Hao J, Bucci J, Cozzi PJ, Kearsley JH, Li Y: Emerging roles of radioresistance in prostate cancer metastasis and radiation therapy. Cancer Metastasis Rev. 2014, 33: 469-496.PubMed
24.
Mulholland DJ, Kobayashi N, Ruscetti M, Zhi A, Tran LM, Huang J, Gleave M, Wu H: Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells. Cancer Res. 2012, 72: 1878-1889.PubMedCentralPubMed
25.
Molina JR, Hayashi Y, Stephens C, Georgescu MM: Invasive glioblastoma cells acquire stemness and increased Akt activation. Neoplasia. 2010, 12: 453-463.PubMedCentralPubMed
26.
Chang L, Graham PH, Hao J, Ni J, Bucci J, Cozzi PJ, Kearsley JH, Li Y: Acquisition of epithelial-mesenchymal transition and cancer stem cell phenotypes is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer radioresistance. Cell Death Dis. 2013, 4: e875-PubMedCentralPubMed
27.
Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, van Roy F, Lee-Kwon W, Donowitz M, Tsichlis PN, Larue L: The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 2003, 63: 2172-2178.PubMed
28.
Aslam MI, Patel M, Singh B, Jameson JS, Pringle JH: MicroRNA manipulation in colorectal cancer cells: from laboratory to clinical application. J Transl Med. 2012, 10: 128-PubMedCentralPubMed
29.
Matsushima K, Isomoto H, Yamaguchi N, Inoue N, Machida H, Nakayama T, Hayashi T, Kunizaki M, Hidaka S, Nagayasu T, Nakashima M, Ujifuku K, Mitsutake N, Ohtsuru A, Yamashita S, Korpal M, Kang Y, Gregory PA, Goodall GJ, Kohno S, Nakao K: MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells. J Transl Med. 2011, 9: 30-PubMedCentralPubMed
30.
Luo X, Dong Z, Chen Y, Yang L, Lai D: Enrichment of ovarian cancer stem-like cells is associated with epithelial to mesenchymal transition through an miRNA-activated AKT pathway. Cell Prolif. 2013, 46: 436-446.PubMed
31.
32.
Courtney KD, Corcoran RB, Engelman JA: The PI3K pathway as drug target in human cancer. J Clin Oncol. 2010, 28: 1075-1083.PubMedCentralPubMed
33.
Engelman JA: Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009, 9: 550-562.PubMed
34.
Steelman LS, Chappell WH, Abrams SL, Kempf RC, Long J, Laidler P, Mijatovic S, Maksimovic-Ivanic D, Stivala F, Mazzarino MC, Donia M, Fagone P, Malaponte G, Nicoletti F, Libra M, Milella M, Tafuri A, Bonati A, Bäsecke J, Cocco L, Evangelisti C, Martelli AM, Montalto G, Cervello M, McCubrey JA: Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging (Albany NY). 2011, 3: 192-222.
35.
Davies MA: Regulation, role, and targeting of Akt in cancer. J Clin Oncol. 2011, 29: 4715-4717.PubMed
36.
Yoeli-Lerner M, Yiu GK, Rabinovitz I, Erhardt P, Jauliac S, Toker A: Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT. Mol Cell. 2005, 20: 539-550.PubMed
37.
Irie HY, Pearline RV, Grueneberg D, Hsia M, Ravichandran P, Kothari N, Natesan S, Brugge JS: Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition. J Cell Biol. 2005, 171: 1023-1034.PubMedCentralPubMed
38.
Girouard J, Lafleur MJ, Parent S, Leblanc V, Asselin E: Involvement of Akt isoforms in chemoresistance of endometrial carcinoma cells. Gynecol Oncol. 2013, 128: 335-343.PubMed
39.
Alqurashi N, Hashimi SM, Wei MQ: Chemical inhibitors and microRNAs (miRNA) targeting the mammalian target of rapamycin (mTOR) pathway: potential for novel anticancer therapeutics. Int J Mol Sci. 2013, 14: 3874-3900.PubMedCentralPubMed
40.
Gulhati P, Bowen KA, Liu J, Stevens PD, Rychahou PG, Chen M, Lee EY, Weiss HL, O’Connor KL, Gao T, Evers BM: mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways. Cancer Res. 2011, 71: 3246-33256.PubMedCentralPubMed
41.
Zeng N, Yang KT, Bayan JA, He L, Aggarwal R, Stiles JW, Hou X, Medina V, Abad D, Palian BM, Al-Abdullah I, Kandeel F, Johnson DL, Stiles BL: PTEN controls β-cell regeneration in aged mice by regulating cell cycle inhibitor p16ink4a. Aging Cell. 2013, 12: 1000-1011.PubMed
42.
Wang H, Zhang G, Zhang H, Zhang F, Zhou B, Ning F, Wang HS, Cai SH, Du J: Acquisition of epithelial-mesenchymal transition phenotype and cancer stem cell-like properties in cisplatin-resistant lung cancer cells through AKT/β-catenin/Snail signaling pathway. Eur J Pharmacol. 2014, 723: 156-166.PubMed
43.
Daikoku T, Hirota Y, Tranguch S, Joshi AR, DeMayo FJ, Lydon JP, Ellenson LH, Dey SK: Conditional loss of uterine Pten unfailingly and rapidly induces endometrial cancer in mice. Cancer Res. 2008, 68: 5619-5627.PubMedCentralPubMed
44.
Lindberg ME, Stodden GR, King ML, MacLean JA, Mann JL, DeMayo FJ, Lydon JP, Hayashi K: Loss of CDH1 and Pten accelerates cellular invasiveness and angiogenesis in the mouse uterus. Biol Reprod. 2013, 89: 8-PubMedCentralPubMed
45.
Chen ML, Xu PZ, Peng XD, Chen WS, Guzman G, Yang X, Di Cristofano A, Pandolfi PP, Hay N: The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/− mice. Genes Dev. 2006, 20: 1569-1574.PubMedCentralPubMed
46.
Salvesen HB, Stefansson I, Kalvenes MB, Das S, Akslen LA: Loss of PTEN expression is associated with metastatic disease in patients with endometrial carcinoma. Cancer. 2002, 94: 2185-2191.PubMed
47.
Terakawa N, Kanamori Y, Yoshida S: Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic factor for patients with endometrial cancer. Endocr Relat Cancer. 2003, 10: 203-208.PubMed
48.
Uegaki K, Kanamori Y, Kigawa J, Kawaguchi W, Kaneko R, Naniwa J, Takahashi M, Shimada M, Oishi T, Itamochi H, Terakawa N: PTEN is involved in the signal transduction pathway of contact inhibition in endometrial cells. Cell Tissue Res. 2006, 323: 523-528.PubMed
49.
Gagnon V, St-Germain ME, Parent S, Asselin E: Akt activity in endometrial cancer cells: regulation of cell survival through cIAP-1. Int J Oncol. 2003, 23: 803-810.PubMed
50.
Cheung LW, Hennessy BT, Li J, Yu S, Myers AP, Djordjevic B, Lu Y, Stemke-Hale K, Dyer MD, Zhang F, Ju Z, Cantley LC, Scherer SE, Liang H, Lu KH, Broaddus RR, Mills GB: High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability. Cancer Discov. 2011, 1: 170-185.PubMedCentralPubMed
51.
Dong P, Xu Z, Jia N, Li D, Feng Y: Elevated expression of p53 gain-of-function mutation R175H in endometrial cancer cells can increase the invasive phenotypes by activation of the EGFR/PI3K/AKT pathway. Mol Cancer. 2009, 8: 103-PubMedCentralPubMed
52.
Hipp S, Walch A, Schuster T, Losko S, Laux H, Bolton T, Höfler H, Becker KF: Activation of epidermal growth factor receptor results in snail protein but not mRNA overexpression in endometrial cancer. J Cell Mol Med. 2009, 13: 3858-3867.PubMedCentralPubMed
53.
Saegusa M, Hashimura M, Kuwata T, Okayasu I: Requirement of the Akt/beta-catenin pathway for uterine carcinosarcoma genesis, modulating E-cadherin expression through the transactivation of slug. Am J Pathol. 2009, 174: 2107-2115.PubMedCentralPubMed
54.
Wu Z, Min L, Chen D, Hao D, Duan Y, Qiu G, Wang Y: Overexpression of BMI-1 promotes cell growth and resistance to cisplatin treatment in osteosarcoma. PLoS One. 2011, 6: e14648-PubMedCentralPubMed
55.
Song LB, Li J, Liao WT, Feng Y, Yu CP, Hu LJ, Kong QL, Xu LH, Zhang X, Liu WL, Li MZ, Zhang L, Kang TB, Fu LW, Huang WL, Xia YF, Tsao SW, Li M, Band V, Band H, Shi QH, Zeng YX, Zeng MS: The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells. J Clin Invest. 2009, 119: 3626-3636.PubMedCentralPubMed
56.
Fan C, He L, Kapoor A, Rybak AP, De Melo J, Cutz JC, Tang D: PTEN inhibits BMI1 function independently of its phosphatase activity. Mol Cancer. 2009, 8: 98-PubMedCentralPubMed
57.
van Vlerken LE, Kiefer CM, Morehouse C, Li Y, Groves C, Wilson SD, Yao Y, Hollingsworth RE, Hurt EM: EZH2 is required for breast and pancreatic cancer stem cell maintenance and can be used as a functional cancer stem cell reporter. Stem Cells Transl Med. 2013, 2: 43-52.PubMedCentralPubMed
58.
Crea F, Fornaro L, Bocci G, Sun L, Farrar WL, Falcone A, Danesi R: EZH2 inhibition: targeting the crossroad of tumor invasion and angiogenesis. Cancer Metastasis Rev. 2012, 31: 753-761.PubMed
59.
Ferraro A, Mourtzoukou D, Kosmidou V, Avlonitis S, Kontogeorgos G, Zografos G, Pintzas A: EZH2 is regulated by ERK/AKT and targets integrin alpha2 gene to control Epithelial-Mesenchymal Transition and anoikis in colon cancer cells. Int J Biochem Cell Biol. 2013, 45: 243-254.PubMed
60.
Benoit YD, Witherspoon MS, Laursen KB, Guezguez A, Beauséjour M, Beaulieu JF, Lipkin SM, Gudas LJ: Pharmacological inhibition of polycomb repressive complex-2 activity induces apoptosis in human colon cancer stem cells. Exp Cell Res. 2013, 319: 1463-1470.PubMed
61.
Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-297.PubMed
62.
Cohn DE, Fabbri M, Valeri N, Alder H, Ivanov I, Liu CG, Croce CM, Resnick KE: Comprehensive miRNA profiling of surgically staged endometrial cancer. Am J Obstet Gynecol. 2010, 202: 656.e1-8.
63.
Hiroki E, Akahira J, Suzuki F, Nagase S, Ito K, Suzuki T, Sasano H, Yaegashi N: Changes in microRNA expression levels correlate with clinicopathological features and prognoses in endometrial serous adenocarcinomas. Cancer Sci. 2010, 101: 241-249.PubMed
64.
Mlcochova J, Faltejskova P, Nemecek R, Svoboda M, Slaby O: MicroRNAs targeting EGFR signalling pathway in colorectal cancer. J Cancer Res Clin Oncol. 2013, 139: 1615-1624.PubMed
65.
Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007, 133: 647-658.PubMedCentralPubMed
66.
Qin X, Yan L, Zhao X, Li C, Fu Y: microRNA-21 overexpression contributes to cell proliferation by targeting PTEN in endometrioid endometrial cancer. Oncol Lett. 2012, 4: 1290-1296.PubMedCentralPubMed
67.
Garofalo M, Di Leva G, Romano G, Nuovo G, Suh SS, Ngankeu A, Taccioli C, Pichiorri F, Alder H, Secchiero P, Gasparini P, Gonelli A, Costinean S, Acunzo M, Condorelli G, Croce CM: miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell. 2009, 16: 498-509.PubMedCentralPubMed
68.
Xia H, Ooi LL, Hui KM: MicroRNA-216a/217-induced epithelial-mesenchymal transition targets PTEN and SMAD7 to promote drug resistance and recurrence of liver cancer. Hepatology. 2013, 58: 629-641.PubMed
69.
Zhang LY, Ho-Fun Lee V, Wong AM, Kwong DL, Zhu YH, Dong SS, Kong KL, Chen J, Tsao SW, Guan XY, Fu L: MicroRNA-144 promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma through repression of PTEN. Carcinogenesis. 2013, 34: 454-463.PubMed
70.
Tian L, Fang YX, Xue JL, Chen JZ: Four microRNAs promote prostate cell proliferation with regulation of PTEN and its downstream signals in vitro. PLoS One. 2013, 8: e75885-PubMedCentralPubMed
71.
Qu C, Liang Z, Huang J, Zhao R, Su C, Wang S, Wang X, Zhang R, Lee MH, Yang H: MiR-205 determines the radioresistance of human nasopharyngeal carcinoma by directly targeting PTEN. Cell Cycle. 2012, 11: 785-796.PubMedCentralPubMed
72.
Karaayvaz M, Zhang C, Liang S, Shroyer KR, Ju J: Prognostic significance of miR-205 in endometrial cancer. PLoS One. 2012, 7: e35158-PubMedCentralPubMed
73.
Wang Y, Tang Q, Li M, Jiang S, Wang X: MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA. Biochem Biophys Res Commun. 2014, 444: 199-204.PubMed
74.
Yu QQ, Wu H, Huang X, Shen H, Shu YQ, Zhang B, Xiang CC, Yu SM, Guo RH, Chen L: MiR-1 targets PIK3CA and inhibits tumorigenic properties of A549 cells. Biomed Pharmacother. 2014, 68: 155-161.PubMed
75.
Fang Y, Xue JL, Shen Q, Chen J, Tian L: MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma. Hepatology. 2012, 55: 1852-1862.PubMed
76.
Urick ME, Rudd ML, Godwin AK, Sgroi D, Merino M, Bell DW: PIK3R1 (p85α) is somatically mutated at high frequency in primary endometrial cancer. Cancer Res. 2011, 71: 4061-4067.PubMedCentralPubMed
77.
Huang X, Shen Y, Liu M, Bi C, Jiang C, Iqbal J, McKeithan TW, Chan WC, Ding SJ, Fu K: Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in diffuse large B-cell lymphoma. Am J Pathol. 2012, 181: 26-33.PubMedCentralPubMed
78.
Guo C, Sah JF, Beard L, Willson JK, Markowitz SD, Guda K: The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Genes Chromosomes Cancer. 2008, 47: 939-946.PubMedCentralPubMed
79.
Noguchi S, Yasui Y, Iwasaki J, Kumazaki M, Yamada N, Naito S, Akao Y: Replacement treatment with microRNA-143 and −145 induces synergistic inhibition of the growth of human bladder cancer cells by regulating PI3K/Akt and MAPK signaling pathways. Cancer Lett. 2013, 328: 353-361.PubMed
80.
Cui W, Zhang S, Shan C, Zhou L, Zhou Z: microRNA-133a regulates the cell cycle and proliferation of breast cancer cells by targeting epidermal growth factor receptor through the EGFR/Akt signaling pathway. FEBS J. 2013, 280: 3962-3974.PubMed
81.
82.
Doghman M, El Wakil A, Cardinaud B, Thomas E, Wang J, Zhao W, Peralta-Del Valle MH, Figueiredo BC, Zambetti GP, Lalli E: Regulation of insulin-like growth factor-mammalian target of rapamycin signaling by microRNA in childhood adrenocortical tumors. Cancer Res. 2010, 70: 4666-4675.PubMedCentralPubMed
83.
Merkel O, Hamacher F, Laimer D, Sifft E, Trajanoski Z, Scheideler M, Egger G, Hassler MR, Thallinger C, Schmatz A, Turner SD, Greil R, Kenner L: Identification of differential and functionally active miRNAs in both anaplastic lymphoma kinase (ALK)+ and ALK- anaplastic large-cell lymphoma. Proc Natl Acad Sci U S A. 2010, 107: 16228-16233.PubMedCentralPubMed
84.
Kong D, Heath E, Chen W, Cher ML, Powell I, Heilbrun L, Li Y, Ali S, Sethi S, Hassan O, Hwang C, Gupta N, Chitale D, Sakr WA, Menon M, Sarkar FH: Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM. PLoS One. 2012, 7: e33729-PubMedCentralPubMed
85.
Cao P, Deng Z, Wan M, Huang W, Cramer SD, Xu J, Lei M, Sui G: MicroRNA-101 negatively regulates Ezh2 and its expression is modulated by androgen receptor and HIF-1alpha/HIF-1beta. Mol Cancer. 2010, 9: 108-PubMedCentralPubMed
86.
Konno Y, Dong P, Xiong Y, Suzuki F, Lu J, Cai M, Watari H, Mitamura T, Hosaka M, Hanley SJ, Kudo M, Sakuragi N: MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells.Oncotarget 2014, [Epub ahead of print].,
87.
Godlewski J, Nowicki MO, Bronisz A, Williams S, Otsuki A, Nuovo G, Raychaudhury A, Newton HB, Chiocca EA, Lawler S: Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 2008, 68: 9125-9130.PubMed
88.
Liu S, Tetzlaff MT, Cui R, Xu X: miR-200c inhibits melanoma progression and drug resistance through down-regulation of BMI-1. Am J Pathol. 2012, 181: 1823-1835.PubMedCentralPubMed
89.
Dong P, Kaneuchi M, Watari H, Hamada J, Sudo S, Ju J, Sakuragi N: MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Mol Cancer. 2011, 10: 99-108.PubMedCentralPubMed
90.
Zhai H, Karaayvaz M, Dong P, Sakuragi N, Ju J: Prognostic significance of miR-194 in endometrial cancer. Biomarker Research. 2013, 1: 12-PubMedCentralPubMed
91.
Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ: The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008, 10: 593-601.PubMed
92.
Dong P, Karaayvaz M, Jia N, Kaneuchi M, Hamada J, Watari H, Sudo S, Ju J, Sakuragi N: Mutant p53 gain-of-function induces epithelial-mesenchymal transition through modulation of the miR-130b-ZEB1 axis. Oncogene. 2013, 32: 3286-3295.PubMedCentralPubMed
93.
Dong P, Kaneuchi M, Watari H, Sudo S, Sakuragi N: MicroRNA-106b modulates epithelial–mesenchymal transition by targeting TWIST1 in invasive endometrial cancer cell lines. Mol Carcinog. 2014, 53: 349-359.PubMed
94.
Kumarswamy R, Mudduluru G, Ceppi P, Muppala S, Kozlowski M, Niklinski J, Papotti M, Allgayer H: MicroRNA-30a inhibits epithelial-to-mesenchymal transition by targeting Snai1 and is downregulated in non-small cell lung cancer. Int J Cancer. 2012, 130: 2044-2053.PubMed
95.
Tominaga E, Yuasa K, Shimazaki S, Hijikata T: MicroRNA-1 targets Slug and endows lung cancer A549 cells with epithelial and anti-tumorigenic properties. Exp Cell Res. 2013, 319: 77-88.PubMed
96.
Liang YJ, Wang QY, Zhou CX, Yin QQ, He M, Yu XT, Cao DX, Chen GQ, He JR, Zhao Q: MiR-124 targets Slug to regulate epithelial-mesenchymal transition and metastasis of breast cancer. Carcinogenesis. 2013, 34: 713-722.PubMedCentralPubMed
97.
Lambertini E, Lolli A, Vezzali F, Penolazzi L, Gambari R, Piva R: Correlation between slug transcription factor and miR-221 in MDA-MB-231 breast cancer cells. BMC Cancer. 2012, 12: 445-PubMedCentralPubMed
98.
Carracedo A, Pandolfi PP: The PTEN–PI3K pathway: of feedbacks and cross-talks. Oncogene. 2008, 27: 5527-5541.PubMed
99.
Guenther MK, Graab U, Fulda S: Synthetic lethal interaction between PI3K/Akt/mTOR and Ras/MEK/ERK pathway inhibition in rhabdomyosarcoma. Cancer Lett. 2013, 337: 200-209.PubMed
100.
Nagaraja AK, Creighton CJ, Yu Z, Zhu H, Gunaratne PH, Reid JG, Olokpa E, Itamochi H, Ueno NT, Hawkins SM, Anderson ML, Matzuk MM: A link between mir-100 and FRAP1/mTOR in clear cell ovarian cancer. Mol Endocrinol. 2010, 24: 447-463.PubMedCentralPubMed
101.
Jiang J, Fridley BL, Feng Q, Abo RP, Brisbin A, Batzler A, Jenkins G, Long PA, Wang L: Genome-wide association study for biomarker identification of rapamycin and Everolimus using a lymphoblastoid cell line system. Front Genet. 2013, 4: 166-PubMedCentralPubMed
102.
103.
Vega S, Morales AV, Ocaña OH, Valdés F, Fabregat I, Nieto MA: Snail blocks the cell cycle and confers resistance to cell death. Genes Dev. 2004, 18: 1131-1143.PubMedCentralPubMed
104.
Tsai JH, Donaher JL, Murphy DA, Chau S, Yang J: Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell. 2012, 22: 725-736.PubMedCentralPubMed
105.
Jamora C, Lee P, Kocieniewski P, Azhar M, Hosokawa R, Chai Y, Fuchs E: A signaling pathway involving TGF-beta2 and snail in hair follicle morphogenesis. PLoS Biol. 2005, 3: e11-PubMedCentralPubMed
106.
Barrallo-Gimeno A, Nieto MA: The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development. 2005, 132: 3151-3161.PubMed
107.
Bae YK, Kim A, Choi JE, Kang SH, Lee SJ: Epithelial-mesenchymal transition phenotype in breast cancers is associated with clinicopathologic factors indicating aggressive biologic behavior and poor clinical outcome.Cancer Res 2012, 72(24 Suppl) Abstract nr P5-04-07.,
108.
Huang RY, Wong MK, Tan TZ, Kuay KT, Ng AH, Chung VY, Chu YS, Matsumura N, Lai HC, Lee YF, Sim WJ, Chai C, Pietschmann E, Mori S, Low JJ, Choolani M, Thiery JP: An EMT spectrum defines an anoikis-resistant and spheroidogenic intermediate mesenchymal state that is sensitive to e-cadherin restoration by a src-kinase inhibitor, saracatinib (AZD0530). Cell Death Dis. 2013, 4: e915-PubMedCentralPubMed
109.
Xie R, Schlumbrecht MP, Shipley GL, Xie S, Bassett RL, Broaddus RR: S100A4 mediates endometrial cancer invasion and is a target of TGF-beta1 signaling. Lab Invest. 2009, 89: 937-947.PubMedCentralPubMed
110.
Dong P, Kaneuchi M, Xiong Y, Cao L, Cai M, Liu X, Guo SW, Ju J, Jia N, Konno Y, Watari H, Hosaka M, Sudo S, Sakuragi N: Identification of KLF17 as a novel epithelial to mesenchymal transition inducer via direct activation of TWIST1 in endometrioid endometrial cancer. Carcinogenesis. 2014, 35: 760-768.PubMed
111.
Tran PT, Shroff EH, Burns TF, Thiyagarajan S, Das ST, Zabuawala T, Chen J, Cho YJ, Luong R, Tamayo P, Salih T, Aziz K, Adam SJ, Vicent S, Nielsen CH, Withofs N, Sweet-Cordero A, Gambhir SS, Rudin CM, Felsher DW: Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis. PLoS Genet. 2012, 8: e1002650-PubMedCentralPubMed
112.
Liu S, Patel SH, Ginestier C, Ibarra I, Martin-Trevino R, Bai S, McDermott SP, Shang L, Ke J, Ou SJ, Heath A, Zhang KJ, Korkaya H, Clouthier SG, Charafe-Jauffret E, Birnbaum D, Hannon GJ, Wicha MS: MicroRNA93 regulates proliferation and differentiation of normal and malignant breast stem cells. PLoS Genet. 2012, 8: e1002751-PubMedCentralPubMed
113.
Sandberg R, Neilson JR, Sarma A, Sharp PA, Burge CB: Proliferating cells express mRNAs with shortened 3′ untranslated regions and fewer microRNA target sites. Science. 2008, 320: 1643-1647.PubMedCentralPubMed
114.
Chin LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, Muller RU, Straka E, Su L, Burki EA, Crowell RE, Patel R, Kulkarni T, Homer R, Zelterman D, Kidd KK, Zhu Y, Christiani DC, Belinsky SA, Slack FJ, Weidhaas JB: A SNP in a let-7 microRNA complementary site in the KRAS 3′ untranslated region increases non-small cell lung cancer risk. Cancer Res. 2008, 68: 8535-8540.PubMedCentralPubMed
115.
Arcaroli JJ, Quackenbush KS, Powell RW, Pitts TM, Spreafico A, Varella-Garcia M, Bemis L, Tan AC, Reinemann JM, Touban BM, Dasari A, Eckhardt SG, Messersmith WA: Common PIK3CA mutants and a novel 3′ UTR mutation are associated with increased sensitivity to saracatinib. Clin Cancer Res. 2012, 18: 2704-2714.PubMed
116.
Perdomo C, Campbell JD, Gerrein J, Tellez CS, Garrison CB, Walser TC, Drizik E, Si H, Gower AC, Vick J, Anderlind C, Jackson GR, Mankus C, Schembri F, O’Hara C, Gomperts BN, Dubinett SM, Hayden P, Belinsky SA, Lenburg ME, Spira A: MicroRNA 4423 is a primate-specific regulator of airway epithelial cell differentiation and lung carcinogenesis. Proc Natl Acad Sci U S A. 2013, 110: 18946-18951.PubMedCentralPubMed
117.
Hu R, Pan W, Fedulov AV, Jester W, Jones MR, Weiss ST, Panettieri RA, Tantisira K, Lu Q: MicroRNA-10a controls airway smooth muscle cell proliferation via direct targeting of the PI3 kinase pathway. FASEB J. 2014, 28: 2347-2357.PubMedCentralPubMed
Metadata
Title
The impact of microRNA-mediated PI3K/AKT signaling on epithelial-mesenchymal transition and cancer stemness in endometrial cancer
Authors
Peixin Dong
Yosuke Konno
Hidemichi Watari
Masayoshi Hosaka
Masayuki Noguchi
Noriaki Sakuragi
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2014
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-014-0231-0

Other articles of this Issue 1/2014

Journal of Translational Medicine 1/2014 Go to the issue

Methodology

Empirical study using network of semantically related associations in bridging the knowledge gap

Research

Metabolomics of Ramadan fasting: an opportunity for the controlled study of physiological responses to food intake

Research

Berberine derivatives reduce atherosclerotic plaque size and vulnerability in apoE−/− mice

Research

Evaluation of clonal origin of malignant mesothelioma

Meeting report

Future perspectives in melanoma research: meeting report from the "Melanoma Bridge", Napoli, December 5th-8th 2013

Research

ShaoYao decoction ameliorates colitis-associated colorectal cancer by downregulating proinflammatory cytokines and promoting epithelial-mesenchymal transition
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits