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Journal of Mammary Gland Biology and Neoplasia
Erschienen in: Journal of Mammary Gland Biology and Neoplasia 2/2019

22.03.2019 | Breast Cancer

Metformin and Breast Cancer: Molecular Targets

verfasst von: J. Faria, G. Negalha, A. Azevedo, F. Martel

Erschienen in: Journal of Mammary Gland Biology and Neoplasia | Ausgabe 2/2019

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Abstract

Metformin has been the first-line drug for the treatment of type II diabetes mellitus for decades, being presently the most widely prescribed antihyperglycemic drug. Retrospective studies associate the use of metformin with a reduction in cancer incidence and cancer-related death. However, despite extensive research about the molecular effects of metformin in cancer cells, its mode of action remains controversial. The major molecular targets of metformin include complex I of the mitochondrial electron transport chain, adenosine monophosphate (AMP)-activated protein kinase (AMPK), and mechanistic target of rapamycin complex 1 (mTORC1), but AMPK-independent effects of metformin have also been described. Breast cancer is one of the leading causes of cancer-related morbidity and mortality among women worldwide. Several studies have reinforced a link between breast cancer risk and diabetes. Moreover, metformin significantly reduces breast cancer risk, compared to patients who are not using metformin and is independent of diabetes status. In this review, we summarize the current molecular evidence to elucidate metformin’s mode of action against breast cancer cells.
Literatur
1.
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of Hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of diabetes. Diabetes Care Am Diabetes Assoc. 2015;38:140–9.
2.
3.
Ortiz-Flores AE, Luque-Ramírez M, Escobar-Morreale HF. Pharmacotherapeutic management of comorbid polycystic ovary syndrome and diabetes. Expert Opin Pharmacother. 2018:1–12.
4.
Finneran MM, Landon MB. Oral agents for the treatment of gestational diabetes. Curr Diab Rep. 2018;18:119.CrossRefPubMed
5.
Ben Sahra I, Le Marchand-Brustel Y, Tanti J-F, Bost F. Metformin in Cancer therapy: a new perspective for an old antidiabetic drug? Mol Cancer Ther. 2010;9:1092–9.CrossRefPubMed
6.
Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease a systematic review. JAMA. 2014;312:2668–75.CrossRefPubMedPubMedCentral
7.
Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B. Metformin: From mechanisms of action to therapies. Cell Metab. Elsevier Inc. 2014;20:953–66.CrossRefPubMed
8.
Schäfer G. Biguanides. A review of history, pharmacodynamics and therapy. Diabetes Metab. 1983;9:148–63.
9.
Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer. 2009;16:1103–23.CrossRefPubMed
10.
Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: a consensus report. Diabetes Care Am Diabetes Assoc. 2010;33:1674–85.
11.
Coughlin SS, Ekwueme DU. Breast cancer as a global health concern. Cancer Epidemiol. 2009;33:315–8.CrossRefPubMed
12.
Youlden DR, Cramb SM, Dunn NAM, Muller JM, Pyke CM, Baade PD. The descriptive epidemiology of female breast cancer: an international comparison of screening, incidence, survival and mortality. Cancer Epidemiol. 2012;36:237–48.CrossRefPubMed
13.
Boyle P, Boniol M, Koechlin A, Robertson C, Valentini F, Coppens K, et al. Diabetes and breast cancer risk: a meta-analysis. Br J Cancer Nature. Publishing Group. 2012;107:1608–17.CrossRef
14.
Evans JMM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330:1304–5.CrossRefPubMedPubMedCentral
15.
Chae YK, Arya A, Malecek M-K, Shin DS, Carneiro B, Chandra S, et al. Repurposing metformin for cancer treatment: current clinical studies. Oncotarget. 2016;7:40767–80.PubMedPubMedCentral
16.
DeCensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A, Bonanni B, et al. Metformin and Cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res. 2010;3:1451–61.
17.
Landman GWD, Kleefstra N, van Hateren KJJ, Groenier KH, Gans ROB, Bilo HJG. Metformin associated with lower Cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care. 2010;33:322–6.CrossRefPubMed
18.
Daugan M, Dufaÿ Wojcicki A, d’Hayer B, Boudy V. Metformin: an anti-diabetic drug to fight cancer. Pharmacol Res. 2016;113:675–85.CrossRefPubMed
19.
Saini N, Yang X. Metformin as an anti-cancer agent: actions and mechanisms targeting cancer stem cells. Acta Biochim Biophys Sin Shanghai. 2018;50:133–43.CrossRefPubMed
20.
Pizzuti L, Vici P, Di Lauro L, Sergi D, Della Giulia M, Marchetti P, et al. Metformin and breast cancer: basic knowledge in clinical context. Cancer Treat Rev Elsevier Ltd. 2015;41:441–7.CrossRefPubMed
21.
Wysocki PJ, Wierusz-Wysocka B. Obesity, hyperinsulinemia and breast cancer: novel targets and a novel role for metformin. Expert Rev Mol Diagn. 2010;10:509–19.CrossRefPubMed
22.
Grossmann ME, Yang DQ, Guo Z, Potter DA, Cleary MP. Metformin treatment for the prevention and/or treatment of breast/mammary tumorigenesis. Curr Pharmacol Rep. 2015;1:312–23.CrossRefPubMedPubMedCentral
23.
Zhao Y, Gong C, Wang Z, Zhang J, Wang L, Zhang S, et al. A randomized phase II study of aromatase inhibitors plus metformin in pre-treated postmenopausal patients with hormone receptor positive metastatic breast cancer. Oncotarget. 2017;8:84224–36.PubMedPubMedCentral
24.
Sonnenblick A, Agbor-Tarh D, Bradbury I, Di Cosimo S, Azim HA, Fumagalli D, et al. Impact of diabetes, insulin, and metformin use on the outcome of patients with human epidermal growth factor receptor 2-positive primary breast cancer: analysis from the ALTTO phase III randomized trial. J Clin Oncol. 2017;35:1421–9.CrossRefPubMedPubMedCentral
25.
Tang GH, Satkunam M, Pond GR, Steinberg GR, Blandino G, Schünemann HJ, et al. Association of metformin with breast cancer incidence and mortality in patients with type 2 diabetes: a GRADE assessed systematic review and meta-analysis. Cancer Epidemiol Biomark Prev. 2018;27:627–35.
26.
Lega IC, Fung K, Lipscombe LL. Metformin use and breast Cancer stage at diagnosis: a population-based study. Diabetes. 2015;64:A439–9.
27.
Hatoum D, McGowan EM. Recent advances in the use of metformin: can treating diabetes prevent breast cancer? Biomed Res Int. 2015;2015:1–13.CrossRef
28.
Pulito C, Donzelli S, Muti P, Puzzo L, Strano S, Blandino G. microRNAs and cancer metabolism reprogramming: the paradigm of metformin. Ann Transl Med. 2014;2:58.PubMedPubMedCentral
29.
Jara JA, López-Muñoz R. Metformin and cancer: between the bioenergetic disturbances and the antifolate activity. Pharmacol Res. 2015;101:102–8.CrossRefPubMed
30.
Quinn BJ, Dallos M, Kitagawa H, Kunnumakkara AB, Memmott RM, Hollander MC, et al. Inhibition of lung tumorigenesis by metformin is associated with decreased plasma IGF-I and diminished receptor tyrosine kinase signaling. Cancer Prev Res. 2013;6:801–10.
31.
Dowling RJO, Lam S, Bassi C, Mouaaz S, Aman A, Kiyota T, et al. Metformin Pharmacokinetics in Mouse Tumors: Implications for Human Therapy. Cell Metab. Elsevier Inc. 2016;23:567–8.CrossRefPubMed
32.
Gong L, Goswami S, Giacomini KM, Altman RB, Klein TE. Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2012;22:820–7.CrossRefPubMedPubMedCentral
33.
Andrzejewski S, Gravel S-P, Pollak M, St-Pierre J. Metformin directly acts on mitochondria to alter cellular bioenergetics. Cancer Metab. 2014;2:12.CrossRefPubMedPubMedCentral
34.
Najafi M, Cheki M, Rezapoor S, Geraily G, Motevaseli E, Carnovale C, et al. Metformin: prevention of genomic instability and cancer: a review. Mutat Res. 2018;827:1–8.
35.
Salminen A, Kauppinen A, Kaarniranta K. AMPK/Snf1 signaling regulates histone acetylation: Impact on gene expression and epigenetic functions. Cell Signal. Elsevier B.V. 2016;28:887–95.CrossRefPubMed
36.
37.
38.
Davila D, Connolly NMC, Bonner H, Weisová P, Dussmann H, Concannon CG, et al. Two-step activation of FOXO3 by AMPK generates a coherent feed-forward loop determining excitotoxic cell fate. Cell Death Differ. 2012;19:1677–88.
39.
Micallef D, Micallef S, Schembri-Wismayer P, Calleja-Agius J. Novel applications of COX-2 inhibitors, metformin, and statins for the primary chemoprevention of breast cancer. J Turk Ger Gynecol Assoc. 2016;17:214–23.CrossRefPubMedPubMedCentral
40.
Queiroz EAIF, Puukila S, Eichler R, Sampaio SC, Forsyth HL, Lees SJ, et al. Metformin induces apoptosis and cell cycle arrest mediated by oxidative stress, AMPK and FOXO3a in MCF-7 breast cancer cells. PLoS One. 2014;9.
41.
Vancura A, Bu P, Bhagwat M, Zeng J, Vancurova I. Metformin as an anticancer agent. Trends Pharmacol Sci. 2018;39:867–78.CrossRefPubMed
42.
Lee JO, Lee SK, Jung JH, Kim JH, You GY, Kim SJ, et al. Metformin induces Rab4 through AMPK and modulates GLUT4 translocation in skeletal muscle cells. J Cell Physiol. 2011;226:974–81.
43.
Stephenne X, Foretz M, Taleux N, van der Zon GC, Sokal E, Hue L, et al. Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status. Diabetologia. 2011;54:3101–10.
44.
Rice S, Pellat L, Ahmetaga A, Bano G, Mason HD, Whitehead SA. Dual effect of metformin on growth inhibition and oestradiol production in breast cancer cells. Int J Mol Med. 2015;35:1088–94.CrossRefPubMed
45.
46.
Madiraju AK, Erion DM, Rahimi Y, Zhang X-M, Braddock DT, Albright RA, et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. NIH Public Access. 2014;510:542–6.CrossRefPubMedPubMedCentral
47.
48.
Morales DR, Morris AD. Metformin in Cancer treatment and prevention. Annu Rev Med. 2015;66:17–29.CrossRefPubMed
49.
Hu T, Chung YM, Guan M, Ma M, Ma J, Berek JS, et al. Reprogramming ovarian and breast cancer cells into non-cancerous cells by low-dose metformin or SN-38 through FOXO3 activation. Sci Rep. 2014;4:1–13.
50.
Kourelis TV, Siegel RD. Metformin and cancer: new applications for an old drug. Med Oncol. 2012;29:1314–27.CrossRefPubMed
51.
Jalving M, Gietema JA, Lefrandt JD, de Jong S, Reyners AKL, Gans ROB, et al. Metformin: taking away the candy for cancer? Eur J Cancer. 2010;46:2369–80.CrossRefPubMed
52.
Yakar S, Adamo ML. Insulin-like growth factor 1 physiology: lessons from mouse models. Endocrinol Metab Clin N Am NIH Public Access. 2012;41:231–47.CrossRef
53.
Chen W, Wang S, Tian T, Bai J, Hu Z, Xu Y, et al. Phenotypes and genotypes of insulin-like growth factor 1, IGF-binding protein-3 and cancer risk: evidence from 96 studies. Eur J Hum Genet. 2009;17:1668–75.
54.
55.
EL-Haggar SM, El-Shitany NA, Mostafa MF, El-Bassiouny NA. Metformin may protect nondiabetic breast cancer women from metastasis. Clin Exp Metastasis. 2016;33:339–57.CrossRefPubMed
56.
Liu B, Fan Z, Edgerton SM, Yang X, Lind SE, Thor AD. Potent anti-proliferative effects of metformin on trastuzumab-resistant breast cancer cells via inhibition of erbB2/IGF-1 receptor interactions. Cell Cycle. 2011;10:2959–66.CrossRefPubMed
57.
Gallagher EJ, LeRoith D. Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Ann N Y Acad Sci. 2011;1243:54–68.CrossRefPubMed
58.
Hall MN. mTOR-What Does It Do? Transplant Proc. Elsevier Inc. 2008;40:5–8.CrossRef
59.
Yoon M. The role of mammalian target of rapamycin (mTOR) in insulin signaling. Nutrients. 2017.
60.
Huang J, Dibble CC, Matsuzaki M, Manning BD. The TSC1-TSC2 complex is required for proper activation of mTOR complex 2. Mol Cell Biol. 2008;28:4104–15.CrossRefPubMedPubMedCentral
61.
Li P, Zhao M, Parris AB, Feng X, Yang X. P53 is required for metformin-induced growth inhibition, senescence and apoptosis in breast cancer cells. Biochem Biophys Res Commun Elsevier Ltd. 2015;464:1267–74.CrossRefPubMed
62.
Zhang J, Li G, Chen Y, Fang L, Guan C, Bai F, et al. Metformin inhibits tumorigenesis and tumor growth of breast cancer cells by upregulating miR-200c but downregulating AKT2 expression. J Cancer. 2017;8:1849–64.
63.
Safe S, Nair V, Karki K. Metformin-induced anticancer activities: recent insights. Biol Chem. 2018;399:321–35.CrossRefPubMed
64.
Wahdan-Alaswad RS, Cochrane DR, Spoelstra NS, Howe EN, Edgerton SM, Anderson SM, et al. Metformin-induced killing of triple-negative breast cancer cells is mediated by reduction in fatty acid synthase via miRNA-193b. Horm Cancer NIH Public Access. 2014;5:374–89.
65.
Yang J, Wei J, Wu Y, Wang Z, Guo Y, Lee P, et al. Metformin induces ER stress-dependent apoptosis through miR-708-5p/NNAT pathway in prostate cancer. Oncogenesis. 2015;4:e158–8.
66.
Li W, Yuan Y, Huang L, Qiao M, Zhang Y. Metformin alters the expression profiles of microRNAs in human pancreatic cancer cells. Diabetes Res Clin Pract. 2012;96:187–95.CrossRefPubMed
67.
Cufí S, Vazquez-Martin A, Oliveras-Ferraros C, Quirantes R, Segura-Carretero A, Micol V, et al. Metformin lowers the threshold for stress-induced senescence: a role for the microRNA-200 family and miR-205. Cell Cycle. 2012;11:1235–46.
68.
Pulito C, Mori F, Sacconi A, Goeman F, Ferraiuolo M, Pasanisi P, et al. Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities. Cell Discov. Nature Publ Group. 2017;3:17022.CrossRefPubMedPubMedCentral
69.
Zhao W, Zhang X, Liu J, Sun B, Tang H, Zhang H. miR-27a-mediated antiproliferative effects of metformin on the breast cancer cell line MCF-7. Oncol Rep. 2016;36:3691–9.CrossRefPubMed
70.
Cabello P, Pineda B, Tormo E, Lluch A, Eroles P. The Antitumor Effect of Metformin Is Mediated by miR-26a in Breast Cancer. Int J Mol Sci. Multidisciplinary Digital Publishing Institute (MDPI). 2016;17:1298.CrossRefPubMedCentral
71.
Cioce M, Valerio M, Casadei L, Pulito C, Sacconi A, Mori F, et al. Metformin-induced metabolic reprogramming of chemoresistant ALDH<sup>bright</sup> breast cancer cells. Oncotarget. 2014;5:4129–43.CrossRefPubMedPubMedCentral
72.
Blandino G, Valerio M, Cioce M, Mori F, Casadei L, Pulito C, et al. Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC. Nat Commun. 2012;3:865.
73.
74.
Marinello PC, da Silva TNX, Panis C, Neves AF, Machado KL, Borges FH, et al. Mechanism of metformin action in MCF-7 and MDA-MB-231 human breast cancer cells involves oxidative stress generation, DNA damage, and transforming growth factor β1 induction. Tumor Biol. 2016;37:5337–46.
75.
76.
Sahin M, Tutuncu NB, Ertugrul D, Tanaci N, Guvener ND. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complicat. 2007;21:118–23.CrossRefPubMed
77.
de Jager J, Kooy A, Lehert P, Wulffelé MG, van der Kolk J, Bets D, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010;340:c2181.CrossRefPubMedPubMedCentral
78.
Ham AC, Enneman AW, van Dijk SC, Oliai Araghi S, Swart KMA, Sohl E, et al. Associations between medication use and homocysteine levels in an older population, and potential mediation by vitamin B12 and folate: data from the B-PROOF study. Drugs Aging. 2014;31:611–21.
79.
Corominas-Faja B, Quirantes-Piné R, Oliveras-Ferraros C, Vazquez-Martin A, Cufí S, Martin-Castillo B, et al. Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs. Aging (Albany NY). 2012;4:480–98.
80.
Janzer A, German NJ, Gonzalez-Herrera KN, Asara JM, Haigis MC, Struhl K. Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells. Proc Natl Acad Sci. 2014;111:10574–9.CrossRefPubMed
81.
Cabreiro F, Au C, Leung K-Y, Vergara-Irigaray N, Cochemé HM, Noori T, et al. Metformin retards aging in C. Elegans by altering microbial folate and methionine metabolism. Cell. 2013;153:228–39.
82.
Dallaglio K, Bruno A, Cantelmo AR, Esposito AI, Ruggiero L, Orecchioni S, et al. Paradoxic effects of metformin on endothelial cells and angiogenesis. Carcinogenesis. 2014;35:1055–66.
83.
84.
Wang J, Li G, Wang Y, Tang S, Sun X, Feng X, et al. Suppression of tumor angiogenesis by metformin treatment via a mechanism linked to targeting of HER2/HIF-1a/VEGF secretion axis. Oncotarget. Impact Journals. 2015;6:44579–92.PubMedPubMedCentral
85.
Falah RR, Talib WH, Shbailat SJ. Combination of metformin and curcumin targets breast cancer in mice by angiogenesis inhibition, immune system modulation and induction of p53 independent apoptosis. Ther Adv Med Oncol. 2017;9:235–52.CrossRefPubMedPubMedCentral
86.
Tadakawa M, Takeda T, Li B, Tsuiji K, Yaegashi N. The anti-diabetic drug metformin inhibits vascular endothelial growth factor expression via the mammalian target of rapamycin complex 1/hypoxia-inducible factor-1α signaling pathway in ELT-3 cells. Mol Cell Endocrinol. 2015;399:1–8.CrossRefPubMed
87.
Deng X-S, Wang S, Deng A, Liu B, Edgerton SM, Lind SE, et al. Metformin targets Stat3 to inhibit cell growth and induce apoptosis in triple-negative breast cancers. Cell Cycle. 2012;11:367–76.
88.
Zhao Z, Cheng X, Wang Y, Han R, Li L, Xiang T, et al. Metformin Inhibits the IL-6-Induced Epithelial-Mesenchymal Transition and Lung Adenocarcinoma Growth and Metastasis. Chellappan SP, editor. PLoS One. 2014;9:e95884.CrossRefPubMedPubMedCentral
89.
90.
Howe LR, Subbaramaiah K, Hudis CA, Dannenberg AJ. Molecular pathways: adipose inflammation as a mediator of obesity-associated Cancer. Clin Cancer Res. 2013;19:6074–83.CrossRefPubMedPubMedCentral
91.
Zheng L, Yang W, Wu F, Wang C, Yu L, Tang L, et al. Prognostic significance of AMPK activation and therapeutic effects of metformin in hepatocellular carcinoma. Clin Cancer Res. 2013;19:5372–80.
92.
Hirsch HA, Iliopoulos D, Struhl K. Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. Proc Natl Acad Sci. 2013;110:972–7.CrossRefPubMed
93.
Foretz M, Andreelli F, Viollet B, Foretz M, Hébrard S, Leclerc J, et al. Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1 / AMPK pathway via a decrease in hepatic energy state. J Clin Invest Find the latest version : Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1 / AMPK pathway via a. 2010;120:2355–69.CrossRefPubMedPubMedCentral
94.
Griss T, Vincent EE, Egnatchik R, Chen J, Ma EH, Faubert B, et al. Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial- Dependent Biosynthesis 2015;1–23.
95.
Kalender A, Selvaraj A, Kim SY, Gulati P, Brule S, Viollet B, et al. Metformin , Independent of AMPK , Inhibits mTORC1 in a Rag GTPase-Dependent Manner. 2010;
96.
Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-peled L, et al. The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1. Science (80- ). 2008;1496–502.
97.
Wu L, Zhou B, Oshiro-rapley N, Gygi SP, Zheng B, Soukas AA, et al. An Ancient, Unified Mechanism for Metformin Growth Inhibition in C . elegans and Cancer. Cell. Elsevier Inc. 2016;167:1705–1711.e13.CrossRefPubMedPubMedCentral
98.
Kwon O, Kwak D, Hoon S, Jeon H, Park M, Chang Y, et al. Nudix-type motif 2 contributes to cancer proliferation through the regulation of Rag GTPase-mediated mammalian target of rapamycin complex 1 localization. Cell Signal. Elsevier Inc. 2017;32:24–35.CrossRefPubMed
99.
Sofer A, Lei K, Johannessen CM, Ellisen LW. Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1. Mol Cell Biol. 2005;25:5834–45.CrossRefPubMedPubMedCentral
100.
Ben SI, Regazzetti C, Robert G, Laurent K, Le Marchand-Brustel Y, Auberger P, et al. Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res. 2011;71:4366–72.CrossRef
101.
Nair V, Sreevalsan S, Basha R, Abdelrahim M, Abudayyeh A. Mechanism of metformin-dependent inhibition of mammalian target of rapamycin ( mTOR ) and Ras activity in pancreatic Cancer ROLE OF SPECIFICITY PROTEIN ( Sp ) TRANSCRIPTION FACTORS *. J Biol Chem. 2014;289:27692–701.CrossRefPubMedPubMedCentral
102.
Beishline K, Azizkhan-Clifford J. Sp1 and the ‘ hallmarks of cancer’. FEBS J. 2015;282:224–58.CrossRefPubMed
103.
Gandhy SU, Imanirad P, Jin U, Nair V, Safe S. Specificity protein (Sp) transcription factors and metformin regulate expression of the long non-coding RNA HULC. Oncotarget. 2015;6:26359–72.CrossRefPubMedPubMedCentral
104.
Wei M, Liu B, Gu Q, Su L, Yu Y, Zhu Z. Stat6 cooperates with Sp1 in controlling breast cancer cell proliferation by modulating the expression of p21 Cip1 / WAF1. Cell Oncol. 2013;36:79–93.CrossRef
105.
Stoner M, Wormke M, Saville B, Samudio I, Qin C, Abdelrahim M, et al. Estrogen regulation of vascular endothelial growth factor gene expression in ZR-75 breast cancer cells through interaction of estrogen receptor a and SP proteins. Oncogene. 2014;23:1052–63.CrossRef
106.
Tian H-P, Lun S-M, Huang H-J, He R, Kong P-Z, Wang Q-S, et al. DNA methylation affects the SP1-regulated transcription of FOXF2 in breast Cancer cells *. J Biol Chem. 2015;290:19173–83.
107.
Sagara Y, Mimori K, Yoshinaga K, Tanaka F, Nishida K, Ohno S, et al. Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer. Br J Cancer. 2004;91:959–65.
108.
Chung Y, Chang C, Wei W, Chang T. Metformin-induced caveolin-1 expression promotes T-DM1 drug efficacy in breast cancer cells. Sci Rep Springer US; 2018;1–9.
109.
Salani B, Maffioli S, Hamoudane M, Parodi A, Ravera S, Passalacqua M, et al. Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells. FASEB J. 2012;26:788–98.
110.
Zimmermann M, Arachchige-Don APS, Donaldson MS, Patriarchi T, Horne MC. Cyclin G2 promotes cell cycle arrest in breast cancer cells responding to fulvestrant and metformin and correlates with patient survival. Cell Cycle. Taylor & Francis. 2016;15:3278–95.CrossRefPubMedPubMedCentral
111.
Amaral I, Silva C, Correia-Branco A, Martel F. Effect of metformin on estrogen and progesterone receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells. Biomed Pharmacother. 2018;102:94–101.CrossRefPubMed
112.
Lohmann AE, Liebman MF, Brien W, Parulekar WR, Gelmon KA, Shepherd LE, et al. Effects of metformin versus placebo on vitamin B12 metabolism in non-diabetic breast cancer patients in CCTG MA.32. Breast Cancer Res Treat. 2017;164:371–8.CrossRefPubMedPubMedCentral
113.
Cuyàs E, Fernández-Arroyo S, Joven J, Menendez JA. Metformin targets histone acetylation in cancer-prone epithelial cells. Cell Cycle. 2016;15:3355–61.CrossRefPubMedPubMedCentral
114.
Cai H, Zhang Y, Han T, Everett RS, Thakker DR. Cation-selective transporters are critical to the AMPK-mediated antiproliferative effects of metformin in human breast cancer cells. Int J Cancer. 2016;138:2281–92.CrossRefPubMed
115.
Lord SR, Cheng WC, Liu D, Gaude E, Haider S, Metcalf T, et al. Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer. Cell Metab. Elsevier Inc. 2018;28:679–88.CrossRefPubMedPubMedCentral
116.
Checkley LA, Rudolph MC, Wellberg EA, Giles ED, Wahdan-Alaswad RS, Houck JA, et al. Metformin accumulation correlates with organic cation transporter 2 protein expression and predicts mammary tumor regression in vivo. Cancer Prev Res. 2017;10:198–207.
117.
118.
Chang YT, Tsai HL, Kung YT, Yeh YS, Huang CW, Ma CJ, et al. Dose-dependent relationship between metformin and colorectal cancer occurrence among patients with Type 2 Diabetes—A nationwide cohort study. Transl Oncol. Elsevier Inc. 2018;11:535–41.CrossRefPubMedPubMedCentral
119.
Aksoy S, Ali M, Sendur N. Demographic and clinico-pathological characteristics in patients with invasive breast cancer receiving metformin. Med Oncol. 2013:5–10.
120.
Castan G, Garcı E, Altzibar JM, Peiro R, Caballero FJ, Ferna T, et al. Association of diabetes and diabetes treatment with incidence of breast cancer. Acta Diabetol. 2016:99–107.
121.
Besic N, Satej N, Ratosa I, Horvat AG, Marinko T, Gazic B, et al. Long-term use of metformin and the molecular subtype in invasive breast carcinoma patients – a retrospective study of clinical and tumor characteristics. BMC Cancer. 2014;14:1–7.CrossRef
122.
Yang H, Peng Y, Ni H, Li Y, Shi Y. Basal autophagy and feedback activation of Akt are associated with resistance to metformin-induced inhibition of hepatic tumor cell growth. PLoS One. 2015:1–12.
123.
Qian RC, Lv J, Li HW, Long YT. Sugar-coated Nanobullet: growth inhibition of Cancer cells induced by metformin-loaded Glyconanoparticles. ChemMedChem. 2017;12:1823–7.CrossRefPubMed
Metadaten
Titel
Metformin and Breast Cancer: Molecular Targets
verfasst von
J. Faria
G. Negalha
A. Azevedo
F. Martel
Publikationsdatum
22.03.2019
Verlag
Springer US
Erschienen in
Journal of Mammary Gland Biology and Neoplasia / Ausgabe 2/2019
Print ISSN: 1083-3021
Elektronische ISSN: 1573-7039
DOI
https://doi.org/10.1007/s10911-019-09429-z

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