Abstract 2969: A Novel pathway for regulation of ANXA2 expression in lung cancer cell metastasis by SETDB1/SMAD3 repressor complex.

Abstract

Abstract Aberrant histone methylation contributes to tumor development and progression by histone methyltransferase. SETDB1 is an H3K9 methyltransferase that contributes to the epigenetic silencing of target genes in cancer cells, but the role of SETDB1 in the progression of tumorigenesis remains largely unknown. We show here that H3K9Me2 and SETDB1 are down-regulated in metastatic lung cancer cell lines. Immunohistochemistry examination of the lung carcinoma tissue microarray revealed that expression of SETDB1 is significant decreased in metastasis status. Ectopic expression of SETDB1 in highly invasive lung cancer cells suppressed cancer cell migration, invasion and filopodia formation. In contrast, knockdown of endogenous SETDB1 in non-invasive lung cancer cells by RNA interference increases cell migration and invasion in vitro. Mechanistic investigations suggested that SETDB1 is specifically down-regulated by miR-29b in metastatic lung cancer cells. Ectopic miR-29b expression in non-invasive lung cancer cells increases cell invasion ability. Furthermore, we also establish a causal role for the SETDB1/SMAD3 complex in driving metastasis and identify ANXA2 as a critical target in this process among numerous target genes. These findings suggest a novel pathway regulated by SETDB1/SMAD3 complex in lung cancer metastasis. Citation Format: Tsai-Yu Tzeng, Ming-Ta Hsu. A Novel pathway for regulation of ANXA2 expression in lung cancer cell metastasis by SETDB1/SMAD3 repressor complex. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2969. doi:10.1158/1538-7445.AM2013-2969