Metformin Downregulates the Insulin/IGF-I Signaling Pathway and Inhibits Different Uterine Serous Carcinoma (USC) Cells Proliferation and Migration in p53-Dependent or -Independent Manners

PLoS ONE

Volumn 8, Issue 4, 2013, Pages

  Sarfstein, Rive ^a   Friedman, Yael ^a   Attias Geva, Zohar ^a   Fishman, Ami ^b   Bruchim, Ilan ^b   Werner, Haim ^a  

^a TEL AVIV UNIVERSITY   (Israel)

^b MEIR MEDICAL CENTER   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOGEN SYNTHASE KINASE 3; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN; MAMMALIAN TARGET OF RAPAMYCIN; METFORMIN; PROTEIN P53; SOMATOMEDIN C; SOMATOMEDIN C RECEPTOR;

ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CELL CYCLE PROGRESSION; CELL MIGRATION; CELL PROLIFERATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFECT; DRUG MECHANISM; ENDOMETRIUM CARCINOMA; FEMALE; G1 PHASE CELL CYCLE CHECKPOINT; G2 PHASE CELL CYCLE CHECKPOINT; HUMAN; HUMAN CELL; MOLECULAR INTERACTION; PROTEIN EXPRESSION; PROTEIN FUNCTION; S PHASE CELL CYCLE CHECKPOINT; SIGNAL TRANSDUCTION; SOMATOMEDIN C RECEPTOR GENE; TUMOR SUPPRESSOR GENE; WILD TYPE;

ADENYLATE KINASE; APOPTOSIS; CELL CYCLE; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; CELL SURVIVAL; CYSTADENOCARCINOMA, SEROUS; DOWN-REGULATION; ENDOMETRIAL NEOPLASMS; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION REGULATION, NEOPLASTIC; GLYCOGEN SYNTHASE KINASE 3; HUMANS; INSULIN; INSULIN-LIKE GROWTH FACTOR I; METFORMIN; PHOSPHORYLATION; PROMOTER REGIONS, GENETIC; RECEPTOR, IGF TYPE 1; RECEPTOR, INSULIN; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEIN P53; UTERINE NEOPLASMS;

EID: 84876423635     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0061537     Document Type: Article

References (59)

1. Kitchener H, (2006) Management of endometrial cancer. Eur J Surg Oncol 32: 838-843.
2. Attias-Geva Z, Bentov I, Kidron D, Amichay K, Sarfstein R, et al. (2012) p53 Regulates insulin-like growth factor-I receptor gene expression in uterine serous carcinoma and predicts responsiveness to an insulin-like growth factor-I receptor-directed targeted therapy. Eur J Cancer 48: 1570-1580.
3. Pallares J, Martinez-Guitarte JL, Dolcet X, Llobet D, Rue M, et al. (2004) Abnormalities in the NF-kappa B family and related proteins in endometrial carcinoma. J Pathol 204: 569-577.
4. Ryan AJ, Susil B, Jobling TW, Oehler MK, (2005) Endometrial cancer. Cell Tissue Res 322: 53-61.
5. Landman GW, van Hateren KJ, Kleefstra N, Groenier KH, Gans RO, et al. (2010) Health-related quality of life and mortality in a general and elderly population of patients with type 2 diabetes (ZODIAC-18). Diabetes Care 33: 2378-2382.
6. Soliman PT, Wu D, Tortolero-Luna G, Schmeler KM, Slomovitz BM, et al. (2006) Association between adiponectin, insulin resistance, and endometrial cancer. Cancer 106: 2376-2381.
7. Liu FS, (2007) Molecular carcinogenesis of endometrial cancer. Taiwan J Obstet Gynecol 46: 26-32.
8. Kaaks R, Lukanova A, Kurzer MS, (2002) Obesity, endogenous hormones, and endometrial cancer risk: A synthetic review. Cancer Epidemiol Biomarkers Prev 11: 1531-1543.
9. Rocha GZ, Dias MM, Ropelle ER, Osorio-Costa F, Rossato FA, et al. (2011) Metformin amplifies chemotherapy-induced AMPK activation and antitumoral growth. Clin Cancer Res 17: 3993-4005.
10. Hadad SM, Fleming S, Thompson AM, (2008) Targeting AMPK: a new therapeutic opportunity in breast cancer. Crit Rev Oncol/Hematol 67: 1-7.
11. Alimova IN, Liu B, Fan Z, Edgerton SM, Dillon T, et al. (2009) Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle 8: 909-915.
12. Guba M, von Breitenbuch P, Steinbauer M, Koehl G, Flegel S, et al. (2002) Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 8: 128-135.
13. Hidalgo M, Rowinsky EK, (2000) The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene 19: 6680-6686.
14. Uhrbom L, Nerio E, Holland EC, (2004) Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model. Nature Med10: 1257-1260.
15. Frost P, Moatamed F, Hoang B, Shi Y, Gera J, et al. (2004) In vivo antitumor effects of the mTOR inhibitor CCI-779 against human multiple myeloma cells in a xenograft model. Blood 104: 4181-4187.
16. Xing D, Orsulic S, (2005) A genetically defined mouse ovarian carcinoma model for the molecular characterization of pathway-targeted therapy and tumor resistance. Proc Natl Acad Sci U S A 102: 6936-6941.
17. Werner H, Bruchim I, (2009) The insulin-like growth factor-I receptor as an oncogene. Arch Physiol Biochem 115: 58-71.
18. Bruchim I, Attias Z, Werner H, (2009) Targeting the IGF1 axis in cancer proliferation. Expert Opin Ther Targets 13: 1179-1192.
19. Cantrell LA, Zhou C, Mendivil A, Malloy KM, Gehrig PA, et al. (2010) Metformin is a potent inhibitor of endometrial cancer cell proliferation-implications for a novel treatment strategy. Gynecol Oncol 116: 92-98.
20. Xie Y, Wang YL, Yu L, Hu Q, Ji L, et al. (2011) Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells. J Steroid Biochem Mol Biol 126: 113-120.
21. Werner H, (2009) For debate: the pathophysiological significance of IGF-I receptor overexpression: new insights. Pediatr Endocrinol Rev 7: 2-5.
22. Bruchim I, Attias Z, Werner H, (2009) Targeting the IGF1 axis in cancer proliferation. Expert Opin Ther Targets 13: 1179-1192.
23. Pollak M, (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nature Rev Cancer 8: 915-928.
24. Werner H, (2012) Tumor suppressors govern insulin-like growth factor signaling pathways: implications in metabolism and cancer. Oncogene 31: 2703-2714.
25. Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Manson JE, et al. (2008) A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. Cancer Epidemiol Biomarkers Prev 17: 921-929.
26. Augustin LS, Polesel J, Bosetti C, Kendall CW, La Vecchia C, et al. (2003) Dietary glycemic index, glycemic load and ovarian cancer risk: a case-control study in Italy. Ann Oncol 14: 78-84.
27. Zhou G, Myers R, Li Y, Chen Y, Shen X, et al. (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108: 1167-1174.
28. Sarfstein R, Bruchim I, Fishman A, Werner H, (2011) The mechanism of action of the histone deacetylase inhibitor vorinostat involves interaction with the insulin-like growth factor signaling pathway. PLoS One 6: e24468.
29. Sarfstein R, Belfiore A, Werner H, (2010) Identification of Insulin-Like Growth Factor-I Receptor (IGF-IR) Gene Promoter-Binding Proteins in Estrogen Receptor (ER)-Positive and ER-Depleted Breast Cancer Cells. Cancers 2: 233-261.
30. Seino S, Seino M, Nishi S, Bell GI, (1989) Structure of the human insulin receptor gene and characterization of its promoter. Proc Natl Acad Sci U S A 86: 114-118.
31. Vindelov LL, Christensen IJ, Nissen NI, (1983) A Detergent-Trypsin Method for the Preparation of Nuclei for Flow Cytometric DNA Analysis. Cytometry 3: 323-327.
32. Bhaskar PT, Hay N, (2007) The two TORCs and Akt. Dev Cell 12: 487-502.
33. Guertin DA, Sabatini DM, (2007) Defining the role of mTOR in cancer. Cancer Cell 12: 9-22.
34. Zakikhani M, Blouin MJ, Piura E, Pollak MN, (2006) Metformin and rapamycin have distinct effects on the AKT pathway and proliferation in breast cancer cells. Breast Cancer Res Treat 123: 271-279.
35. Sarfstein R, Maor S, Reizner N, Abramovitch S, Werner H, (2006) Transcriptional regulation of the insulin-like growth factor-1 receptor in breast cancer. Mol Cell Endocrinol 252: 241-246.
36. Kiang JG, Bowman PD, Wu BW, Hampton N, Kiang AG, et al. (2004) Geldanamycin treatment inhibits hemorrhage-induced increases in KLF6 and iNOS expression in unresuscitated mouse organs: role of inducible HSP70. J Appl Physiol 97: 564-569.
37. Choi SH, Kim YW, Kim SG, (2010) AMPK-mediated GSK3beta inhibition by isoliquiritigenin contributes to protecting mitochondria against iron-catalyzed oxidative stress. Biochem Pharmacol 79: 1352-1362.
38. Ciaraldi TP, Oh DK, Christiansen L, Nikoulina SE, Kong AP, et al. (2006) Tissue-specific expression and regulation of GSK-3 in human skeletal muscle and adipose tissue. Am J Physiol Endocrinol Metab 291: E891-898.
39. Song J, Ren P, Zhang L, Wang XL, Chen L, et al. (2010) Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4. Biochem Bioph Res Commun 393: 89-94.
40. Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, et al. (2009) New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 32: 1620-1625.
41. Currie CJ, Poole CD, Gale EA, (2009) The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 52: 1766-1777.
42. Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, et al. (2009) Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 27: 3297-3302.
43. Dong L, Zhou Q, Zhang Z, Zhu Y, Duan T, et al. (2012) Metformin sensitizes endometrial cancer cells to chemotherapy by repressing glyoxalase I expression. J Obstet Gynaecol Res 38: 1077-1085.
44. Hanna RK, Zhou C, Malloy KM, Sun L, Zhong Y, et al. (2012) Metformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway. Gynecol Oncol 125: 458-469.
45. Hollstein M, Sidransky D, Vogelstein B, Harris CC, (1991) p53 mutations in human cancers. Science 253: 49-53.
46. Jin X, Gossett DR, Wang S, Yang D, Cao Y, et al. (2004) Inhibition of AKT survival pathway by a small molecule inhibitor in human endometrial cancer cells. Br J Cancer 91: 1808-1812.
47. Reynolds RK, Hu C, Baker VV, (1998) Transforming growth factor-alpha and insulin-like growth factor-I, but not epidermal growth factor, elicit autocrine stimulation of mitogenesis in endometrial cancer cell lines. Gynecol Oncol 70: 202-209.
48. Kang-Park S, Lee YI, Lee YI, (2003) PTEN modulates insulin-like growth factor II (IGF-II)-mediated signaling; the protein phosphatase activity of PTEN downregulates IGF-II expression in hepatoma cells. FEBS Lett 545: 203-208.
49. Zhao H, Dupont J, Yakar S, Karas M, LeRoith D, (2004) PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. Oncogene 23: 786-794.
50. Korch C, Spillman MA, Jackson TA, Jacobsen BM, Murphy SK, et al. (2012) DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination. Gynecol Oncol 127: 241-248.
51. Santin AD, Zhan F, Cane S, Bellone S, Palmieri M, et al. (2005) Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy. Br J Cancer 92: 1561-1573.
52. Attias-Geva Z, Bentov I, Ludwig DL, Fishman A, Bruchim I, et al. (2011) Insulin-like growth factor-I receptor (IGF-IR) targeting with monoclonal antibody cixutumumab (IMC-A12) inhibits IGF-I action in endometrial cancer cells. Eur J Cancer 47: 1717-1726.
53. Zhuang Y, Miskimins WK, (2008) Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1. J Mol Signal 3: 18.
54. Bost F, Sahra IB, Le Marchand-Brustel Y, Tanti J-F, (2012) Metformin and cancer therapy. Curr Opin Oncol 24: 103-108.
55. Vivanco I, Sawyers CL, (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2: 489-501.
56. Bjornsti MA, Houghton PJ, (2004) The TOR pathway: a target for cancer therapy. Nat Rev Cancer 4: 335-348.
57. Oldham S, Hafen E, (2003) Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol 13: 79-85.
58. Beurel E, Kornprobst M, Blivet-Van Eggelpoel MJ, Ruiz-Ruiz C, Cadoret A, et al. (2004) GSK-3beta inhibition by lithium confers resistance to chemotherapy-induced apoptosis through the repression of CD95 (Fas/APO-1) expression. Exp Cell Res 300: 354-364.
59. Liu S, Yu S, Hasegawa Y, Lapushin R, Xu HJ, et al. (2004) Glycogen synthase kinase 3beta is a negative regulator of growth factor-induced activation of the c-Jun N-terminal kinase. J Biol Chem 279: 51075-51081.