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MYC suppresses cancer metastasis by direct transcriptional silencing of αv and β3 integrin subunits
Open accessAbstract
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 αvβ3 integrin, and that exogenous expression of β3 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.
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“A recent report has found that MYC overexpression leads to a direct downregulation of ITGB3, inducing decreased motility and invasiveness (Liu et al., 2012).”
From Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway (2017) · cites this paper as Liu et al., 2012
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Metadata
- Authors
- Liu, H., Radisky, D. C., Yang, D., Xu, R., Radisky, E. S., Bissell, M. J., & Bishop, J. M.
- Affiliations
- University of California, San Francisco (US)
- Mayo Clinic in Florida (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Radisky, Derek C.
- Venue
- Nature Cell Biology
- Published
- 2012-05-13
- Volume
- 14
- Issue
- 6
- Pages
- 567-574
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC3366024
- OpenAlex
- W1480621946
- Cited by
- 181
- References
- 51
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 7 · 2021: 8 · 2020: 12 · 2019: 6 · 2018: 24 · 2017: 16 · 2016: 12 · 2015: 19 · 2014: 25 · 2013: 18 · 2012: 6
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA122086, U54CA126552, CA-116201, R01CA122086, U54CA143836, R37CA064786, U01CA143233, P50CA091956, P50CA116201)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- c-Myc, metastasis suppression, integrin αvβ3, CD61, ITGAV, transcriptional repression, cell migration, cell invasion, breast cancer, lung metastasis, liver metastasis, tumor xenografts
- MeSH terms
- Animals, Extracellular Matrix, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Transcription, Genetic, Proto-Oncogene Proteins c-myc, Gene Silencing, Protein Subunits, Integrin alpha5, Integrin beta3, Cell Line, Tumor, Mice
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