American Association for Cancer Research
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Supplemental Figure S5 from H3K9 Histone Methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 Pathway to Suppress Lung Cancer Metastasis

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posted on 2023-03-30, 22:49 authored by 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

ANXA2 and SMAD3 promotes F-actin polymerization formation in lung cancer cells.

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ARTICLE 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. Cancer Res; 74(24); 7333–43. ©2014 AACR.