IKK? Suppression of TSC1 Links Inflammation and Tumor Angiogenesis via the mTOR Pathway

ASIA unversity > 醫學暨健康學院 > 生物科技學系 > 期刊論文 > Item 310904400/4578

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題名:	IKK? Suppression of TSC1 Links Inflammation and Tumor Angiogenesis via the mTOR Pathway
作者:	Dung-Fang Lee;Hsu-Ping Kuo;Chun-Te Chen;Jung-Mao Hsu;Chao-Kai Chou;Yongkun Wei;Hui-Lung Sun;Long-Yuan Li;Bo Ping;Wei-Chien Huang;Xianghuo He;Jen-Yu Hung;Chien-Chen Lai;Qinqing Ding;Jen-Liang Su;Jer-Yen Yang;Aysegul A. Sahin;Gabriel N. Hortobagyi;Fuu-Jen Tsai;Chang-Hai Tsai;Mien-Chie Hung
日期:	2007-04
上傳時間:	2009-11-27 05:56:54 (UTC+0)
出版者:	Asia University
摘要:	TNF? has recently emerged as a regulator linking inflammation to cancer pathogenesis, but the detailed cellular and molecular mechanisms underlying this link remain to be elucidated. The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function may contribute to tumorigenesis. Here we show that IKK?, a major downstream kinase in the TNF? signaling pathway, physically interacts with and phosphorylates TSC1 at Ser487 and Ser511, resulting in suppression of TSC1. The IKK?-mediated TSC1 suppression activates the mTOR pathway, enhances angiogenesis, and results in tumor development. We further find that expression of activated IKK? is associated with TSC1 Ser511 phosphorylation and VEGF production in multiple tumor types and correlates with poor clinical outcome of breast cancer patients. Our findings identify a pathway that is critical for inflammation-mediated tumor angiogenesis and may provide a target for clinical intervention in human cancer.
關聯:	CELL 130(3):440-455
顯示於類別:	[生物科技學系] 期刊論文

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