RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of Aurora-A and BRCA2 in midbody during cytokinesis

Gong Yang, Imelda Mercado-Uribe, Asha S. Multani, Subrata Sen, Ie Ming Shih, Kwong Kwok Wong, David M. Gershenson, Jinsong Liu

Research output: Contribution to journalArticle


The oncogene RAS is known to induce genomic instability, leading to cancer development; the underlying mechanism, however, remains poorly understood. To better understand how RAS functions, we measured the activity of the functionally related genes Aurora-A and BRCA2 in ovarian cancer cell lines and tumor samples containing RAS mutations. We found that Aurora-A and BRCA2 inversely controlled RAS-associated genomic instability and ovarian tumorigenesis through regulation of cytokinesis and polyploidization. Overexpression of mutated RAS ablated BRCA2 expression but induced Aurora-A accumulation at the midbody, leading to abnormal cytokinesis and ultimately chromosomal instability via polyploidy in cancer cells. RAS regulates the expression of Aurora-A and BRCA2 through dysregulated protein expression of farnesyl protein transferase β and insulin-like growth factor binding protein 3. Our results suggest that the imbalance in expression of Aurora-A and BRCA2 regulates RAS-induced genomic instability and tumorigenesis.

Original languageEnglish (US)
Pages (from-to)275-285
Number of pages11
JournalInternational Journal of Cancer
Issue number2
StatePublished - Jul 15 2013



  • Aurora-A
  • BRCA2
  • cytokinesis
  • genomic instability
  • polyploid cancer cells
  • RAS

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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