YEATS4 is a novel oncogene amplified in non-small cell lung cancer that regulates the p53 pathway

Larissa A. Pikor, William W. Lockwood, Kelsie L. Thu, Emily A. Vucic, Raj Chari, Adi F. Gazdar, Stephen Lam, Wan L. Lam

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19 Scopus citations

Abstract

Genetic analyses of lung cancer have helped found new treatments in this disease. Weconducted an integrative analysis of gene expression and copy number in 261 non-small cell lung cancers (NSCLC) relative to matched normal tissues to define novel candidate oncogenes, identifying 12q13-15 and more specifically the YEATS4 gene as amplified and overexpressed in ~20% of the NSCLC cases examined. Overexpression of YEATS4 abrogated senescence in human bronchial epithelial cells. Conversely, RNAi-mediated attenuation of YEATS4 in human lung cancer cells reduced their proliferation and tumor growth, impairing colony formation and inducing cellular senescence. These effects were associated with increased levels of p21WAF1 and p53 and cleavage of PARP, implicating YEATS4 as a negative regulator of the p21-p53 pathway. We also found that YEATS4 expression affected cellular responses to cisplastin, with increased levels associated with resistance and decreased levels with sensitivity. Taken together, our findings reveal YEATS4 as a candidate oncogene amplified in NSCLC, and a novel mechanism contributing to NSCLC pathogenesis.

Original languageEnglish (US)
Pages (from-to)7301-7312
Number of pages12
JournalCancer Research
Volume73
Issue number24
DOIs
StatePublished - Dec 15 2013

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pikor, L. A., Lockwood, W. W., Thu, K. L., Vucic, E. A., Chari, R., Gazdar, A. F., Lam, S., & Lam, W. L. (2013). YEATS4 is a novel oncogene amplified in non-small cell lung cancer that regulates the p53 pathway. Cancer Research, 73(24), 7301-7312. https://doi.org/10.1158/0008-5472.CAN-13-1897