H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis

Pei Chun Wu, Jeng Wei Lu, Jer Yen Yang, I. Hsuan Lin, Da Liang Ou, Yu Hsiang Lin, Kuan Hsien Chou, Wen Feng Huang, Wan Ping Wang, Yih Leh Huang, Chiun Hsu, Liang In Lin, Yueh Min Lin, C. K. James Shen, Tsai Yu Tzeng

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Aberrant histone methylation is a frequent event during tumor development and progression. KMT1E (also known as SETDB1) is a histone H3K9 methyltransferase that contributes to epigenetic silencing of both oncogenes and tumor suppressor genes in cancer cells. In this report, we demonstrate that KMT1E acts as a metastasis suppressor that is strongly downregulated in highly metastatic lung cancer cells. Restoring KMT1E expression in this setting suppressed filopodia formation, migration, and invasive behavior. Conversely, loss of KMT1E in lung cancer cells with limited metastatic potential promoted migration in vitro and restored metastatic prowess in vivo. Mechanistic investigations indicated that KMT1E cooperates with the TGFβ-regulated complex SMAD2/3 to repress metastasis through ANXA2. Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFβ-mediated lung cancer metastasis.

Original languageEnglish
Pages (from-to)7333-7343
Number of pages11
JournalCancer Research
Volume74
Issue number24
DOIs
Publication statusPublished - Dec 15 2014
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Wu, P. C., Lu, J. W., Yang, J. Y., Lin, I. H., Ou, D. L., Lin, Y. H., Chou, K. H., Huang, W. F., Wang, W. P., Huang, Y. L., Hsu, C., Lin, L. I., Lin, Y. M., James Shen, C. K., & Tzeng, T. Y. (2014). H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis. Cancer Research, 74(24), 7333-7343. https://doi.org/10.1158/0008-5472.CAN-13-3572