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	A role of Rab7 in stabilizing EGFR-Her2 and in sustaining Akt survival signal
	Wang, Tuanlao ; Zhang, Ming ; Ma, Zexu ; Guo, Ke ; Tergaonkar, Vinay ; Zeng, Qi ; Hong, Wanjin ; Hong WJ(洪万进)
	2012-06
关键词	EPIDERMAL-GROWTH-FACTOR CELL LUNG-CANCER NUTRIENT TRANSPORTER EXPRESSION ANCHORAGE-INDEPENDENT GROWTH RECEPTOR TYROSINE KINASES PROTEIN-DEGRADATION LENTIVIRAL VECTORS GERANYLGERANYL TRANSFERASE MOLECULAR CHAPERONE ENDOCYTIC PATHWAY
英文摘要	Rab7 plays an important role in regulating endocytic traffic. In view of an emerging role of membrane traffic in signaling and diseases, we have examined the possible role of Rab7 in oncogenesis. The role of Rab7 was investigated using shRNA-mediated knockdown in A431 and MCF7 cancer cells. To our surprise, Rab7 knockdown effectively suppressed anchorage-independent growth of cancer cells in soft agar. Anoikis (matrix-detachment triggered apoptosis) was enhanced, while the level of phosphorylated (active) Akt (which is a key survival factor) was significantly reduced. Also intriguing was the observation that EGFR and Her2 levels were significantly reduced when Rab7 was knocked-down. More robust reduction of EGFR and Her2 levels was observed when knocked-down cells were treated with HSP90 inhibitor geldanamycin (GA). Low concentration of GA (50100?nm)-induced apoptosis of the Rab7 knocked-down cells but not control cells, suggesting that Rab7 and HSP90 together contribute to the optimal stability of EGFR and Her2 as well as to protect cancer cells from apoptosis. Rab7 seems to protect EGFR and Her2 from proteosome-mediated degradation. These results suggest that Rab7 is likely involved in protecting EGFR and Her2 from being degraded by the proteosome and in maintaining optimal Akt survival signal (especially during cell detachment or when HSP90 is inhibited). Rab7 is potentially a novel target for combinatory therapy with Hsp90 inhibitors. J. Cell. Physiol. 227: 27882797, 2012. (c) 2011 Wiley Periodicals, Inc.; National Natural Science foundation of China [30928011, 30971442, 31071176]; National 973 prophase grant of China [2010CB535000]; Natural Science Foundation of Fujian Province of China
语种	英语
出版者	WILEY-BLACKWELL
内容类型	期刊论文
源URL	[http://dx.doi.org/10.1002/jcp.23023]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Wang, Tuanlao,Zhang, Ming,Ma, Zexu,et al. A role of Rab7 in stabilizing EGFR-Her2 and in sustaining Akt survival signal[J],2012.
APA	Wang, Tuanlao.,Zhang, Ming.,Ma, Zexu.,Guo, Ke.,Tergaonkar, Vinay.,...&洪万进.(2012).A role of Rab7 in stabilizing EGFR-Her2 and in sustaining Akt survival signal..
MLA	Wang, Tuanlao,et al."A role of Rab7 in stabilizing EGFR-Her2 and in sustaining Akt survival signal".(2012).

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