RAS As Supporting Actor in Breast Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2019 Nov 30

PMID 31781501

Citations 33

Authors

Mirco Galie

Affiliations

Soon will be listed here.

Abstract

Oncogenic activation of RAS isoforms leads tumor initiation and progression in many types of cancers and is gaining increasing interest as target for novel therapeutic strategies. In sharp contrast with other types of cancer, the importance of RAS in breast tumorigenesis has long been undermined by the low frequency of its oncogenic mutation in human breast lesions. Nevertheless, a wealth of studies over the last years have revealed how the engagement of RAS function might be mandatory downstream varied oncogenic alterations for the progression, metastatic dissemination, and therapy resistance in breast cancers. We review herein the major studies over the last three decades which have explored the controversial role of RAS proteins and their mutation status in breast tumorigenesis and have contributed to reveal their role as supporting actors, instead of as primary cause, in breast cancer.

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References

Elenbaas B, Spirio L, Koerner F, Fleming M, Zimonjic D, Donaher J . Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes Dev. 2001; 15(1):50-65. PMC: 312602. DOI: 10.1101/gad.828901. View

Leblanc V, Delumeau I, Tocque B . Ras-GTPase activating protein inhibition specifically induces apoptosis of tumour cells. Oncogene. 1999; 18(34):4884-9. DOI: 10.1038/sj.onc.1202855. View

Smith C, Pollice A, Gu L, Brown K, Singh S, Janocko L . Correlations among p53, Her-2/neu, and ras overexpression and aneuploidy by multiparameter flow cytometry in human breast cancer: evidence for a common phenotypic evolutionary pattern in infiltrating ductal carcinomas. Clin Cancer Res. 2000; 6(1):112-26. View

Swarbrick A, Roy E, Allen T, Bishop J . Id1 cooperates with oncogenic Ras to induce metastatic mammary carcinoma by subversion of the cellular senescence response. Proc Natl Acad Sci U S A. 2008; 105(14):5402-7. PMC: 2291136. DOI: 10.1073/pnas.0801505105. View

Liu M, Casimiro M, Wang C, Shirley L, Jiao X, Katiyar S . p21CIP1 attenuates Ras- and c-Myc-dependent breast tumor epithelial mesenchymal transition and cancer stem cell-like gene expression in vivo. Proc Natl Acad Sci U S A. 2009; 106(45):19035-9. PMC: 2776463. DOI: 10.1073/pnas.0910009106. View

Okada T, Sinha S, Esposito I, Schiavon G, Lopez-Lago M, Su W . Author Correction: The Rho GTPase Rnd1 suppresses mammary tumorigenesis and EMT by restraining Ras-MAPK signalling. Nat Cell Biol. 2019; 21(4):534. DOI: 10.1038/s41556-019-0288-3. View

Zheng Z, Tian L, Bu W, Fan C, Gao X, Wang H . Wild-Type N-Ras, Overexpressed in Basal-like Breast Cancer, Promotes Tumor Formation by Inducing IL-8 Secretion via JAK2 Activation. Cell Rep. 2015; 12(3):511-24. PMC: 4512851. DOI: 10.1016/j.celrep.2015.06.044. View

Tront J, Hoffman B, Liebermann D . Gadd45a suppresses Ras-driven mammary tumorigenesis by activation of c-Jun NH2-terminal kinase and p38 stress signaling resulting in apoptosis and senescence. Cancer Res. 2006; 66(17):8448-54. DOI: 10.1158/0008-5472.CAN-06-2013. View

Bos J, Fearon E, Hamilton S, Verlaan-de Vries M, VAN Boom J, Van Der Eb A . Prevalence of ras gene mutations in human colorectal cancers. Nature. 1987; 327(6120):293-7. DOI: 10.1038/327293a0. View

10.

Wang S, Liu J, Ju Y, Pellecchia G, Voisin V, Wang D . microRNA-143/145 loss induces Ras signaling to promote aggressive Pten-deficient basal-like breast cancer. JCI Insight. 2017; 2(15). PMC: 5543917. DOI: 10.1172/jci.insight.93313. View

11.

Mirzoeva O, Das D, Heiser L, Bhattacharya S, Siwak D, Gendelman R . Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition. Cancer Res. 2009; 69(2):565-72. PMC: 2737189. DOI: 10.1158/0008-5472.CAN-08-3389. View

12.

Wulf G, Ryo A, Wulf G, Lee S, Niu T, Petkova V . Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1. EMBO J. 2001; 20(13):3459-72. PMC: 125530. DOI: 10.1093/emboj/20.13.3459. View

13.

McGlynn L, Kirkegaard T, Edwards J, Tovey S, Cameron D, Twelves C . Ras/Raf-1/MAPK pathway mediates response to tamoxifen but not chemotherapy in breast cancer patients. Clin Cancer Res. 2009; 15(4):1487-95. DOI: 10.1158/1078-0432.CCR-07-4967. View

14.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

15.

Larive R, Moriggi G, Menacho-Marquez M, Canamero M, de Alava E, Alarcon B . Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease. Nat Commun. 2014; 5:3881. DOI: 10.1038/ncomms4881. View

16.

Cerrito M, Galbaugh T, Wang W, Chopp T, Salomon D, Cutler M . Dominant negative Ras enhances lactogenic hormone-induced differentiation by blocking activation of the Raf-Mek-Erk signal transduction pathway. J Cell Physiol. 2004; 201(2):244-58. PMC: 1586098. DOI: 10.1002/jcp.20077. View

17.

Zhang J, Liu X, Datta A, Govindarajan K, Tam W, Han J . RCP is a human breast cancer-promoting gene with Ras-activating function. J Clin Invest. 2009; 119(8):2171-83. PMC: 2719918. DOI: 10.1172/JCI37622. View

18.

Jin W, Wu L, Liang K, Liu B, Lu Y, Fan Z . Roles of the PI-3K and MEK pathways in Ras-mediated chemoresistance in breast cancer cells. Br J Cancer. 2003; 89(1):185-91. PMC: 2394213. DOI: 10.1038/sj.bjc.6601048. View

19.

Papke B, Der C . Drugging RAS: Know the enemy. Science. 2017; 355(6330):1158-1163. DOI: 10.1126/science.aam7622. View

20.

Kim H, Choi J, Kim J . Ras promotes transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition via a leukotriene B4 receptor-2-linked cascade in mammary epithelial cells. J Biol Chem. 2014; 289(32):22151-60. PMC: 4139228. DOI: 10.1074/jbc.M114.556126. View