MYC suppresses cancer metastasis by direct transcriptional silencing of α v and β 3 integrin subunits

Hong Liu, Derek C. Radisky, Dun Yang, Ren Xu, Evette S. Radisky, Mina J. Bissell, J. Michael Bishop

Research output: Contribution to journalArticlepeer-review

158 Scopus citations

Abstract

Overexpression of MYC transforms cells in culture, elicits malignant tumours in experimental animals and is found in many human tumours. We now report the paradoxical finding that this powerful oncogene can also act as a suppressor of cell motility, invasiveness and metastasis. Overexpression of MYC stimulated proliferation of breast cancer cells both in culture and in vivo as expected, but inhibited motility and invasiveness in culture, and lung and liver metastases in xenografted tumours. We show further that MYC represses transcription of both subunits of α vβ 3 integrin, and that exogenous expression of β 3 integrin in human breast cancer cells that do not express this integrin rescues invasiveness and migration when MYC is downregulated. These data uncover an unexpected function of MYC, provide an explanation for the hitherto puzzling literature on the relationship between MYC and metastasis, and reveal a variable that could influence the development of therapies that target MYC.

Original languageEnglish
Pages (from-to)567-574
Number of pages8
JournalNature Cell Biology
Volume14
Issue number6
DOIs
StatePublished - Jun 2012

Bibliographical note

Funding Information:
assay, E. Miller for work with the orthotopic animal assay, M. Cichon for cloning constructs and M. Stallings-Mann for work with analysis of experiments. We also thank members of the Bishop, Bissell and Radisky laboratories for their constructive discussion and help. This work was financially supported initially by the George Williams Hooper Foundation (J.M.B.). The founder had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Further support came from NIH (P50 CA091956) and the DoD (PC094054) (to E.S.R.); NCI CA122086, Susan B. Komen foundation grant FAS0703855 and the Mayo Clinic Breast Cancer SPORE grant CA116201 (to D.C.R.); the DoD (W81XWH0810736), NIH/NCI (R37CA064786, U01CA143233, U54CA143836 and U54CA126552) and the Department of Energy OBER Low Dose Radiation Program (contract no. DE-AC02-05CH1123) (to M.J.B.).

ASJC Scopus subject areas

  • Cell Biology

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