Induction of c-Cbl contributes to anti-cancer effects of HDAC inhibitor in lung cancer

Tzu Tang Wei, Yu Chin Lin, Pei Hua Lin, Jin Yuan Shih, Chia Wei Chou, Wei Jan Huang, Yu Chih Yang, Pei Wen Hsiao, Ching Chow Chen

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Here we found loss of c-Cbl, an E3 ligase, expression in non-small cell lung cancer (NSCLC) compared with its adjacent normal tissue in patient specimens. HDAC inhibition by WJ or knockdown of HDAC 1, HDAC2, HDAC3 or HDAC6 all induced c-Cbl. Ectopic expression of c-Cbl induced decreased EGFR, inhibited growth in NSCLC cells. Knockdown of EGFR inhibited NSCLC growth. Mutation of EGFR at Y1045 decreased WJ-induced growth inhibition as well as in vivo anti-cancer effect and EGFR degradation mediated by WJ. Time-lapse confocal analysis showed co-localization of c-Cbl and EGFR after WJ treatment. Furthermore, WJ inhibited lung tumor growth through c-Cbl induction in orthotopic and tail vein injected models. C-Cbl up-regulation induced by HDACi is a potential strategy for NSCLC treatment.

Original languageEnglish
Pages (from-to)12481-12492
Number of pages12
JournalOncotarget
Volume6
Issue number14
Publication statusPublished - 2015

Keywords

  • C-Cbl
  • EGFR
  • HDAC inhibitors
  • Lung cancer

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Wei, T. T., Lin, Y. C., Lin, P. H., Shih, J. Y., Chou, C. W., Huang, W. J., Yang, Y. C., Hsiao, P. W., & Chen, C. C. (2015). Induction of c-Cbl contributes to anti-cancer effects of HDAC inhibitor in lung cancer. Oncotarget, 6(14), 12481-12492.