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Cell Death and Disease:厦门大学药学院王团老教授课题组发表肿瘤研究文章

摘要 : 2015年10月15日,Nature出版集团旗下子刊《Cell Death&Disease》期刊上在线发表了厦门大学药学院王团老教授课题组的一项研究文章,文章揭示囊泡运输通过信号传导影响细胞迁移、侵袭和肿瘤发生的机制

 2015年10月15日,Nature出版集团旗下子刊《Cell Death&Disease》期刊上在线发表了厦门大学药学院王团老教授课题组的一项研究文章,文章揭示囊泡运输通过信号传导影响细胞迁移、侵袭和肿瘤发生的机制,文章题为“RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS”。

囊泡运输不仅调控细胞内蛋白质的定向运输,同时也调节细胞内信号传导,从而影响细胞迁移、侵袭和肿瘤发生。小分子GTP酶(Rab蛋白)Rab7的效应因子RILP是调节晚期内体/溶酶体蛋白质运输过程的关键因子。王团老教授课题组的研究发现,过度表达RILP抑制乳腺癌细胞的迁移、侵袭,研究结果揭示了RILP通过与Ras/Ral信号通路中的RalGDS因子相互作用,调节小G蛋白RalA的活性,从而抑制肿瘤细胞侵袭的分子机制。

图 RILP与RalGDS互作抑制细胞侵袭的机制

原文链接:

RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS

原文摘要:

RILP (Rab7-interacting lysosomal protein) is a key regulator for late endosomal/lysosomal trafficking, and probably a tumor suppressor in prostate cancer. However, the role of RILP in other cancers and the underlying mechanism for RILP in regulating the invasion of cancer cells remain to be investigated. In this study, we showed that overexpression of RILP in breast cancer cells inhibits the migration and invasion, wheras the depletion of RILP by RNAi-mediated knockdown promotes the migration and invasion. We identified RalGDS (Ral guanine nucleotide dissociation stimulator) as a novel interacting partner for RILP, and truncation analysis revealed the N-terminal region of RILP is responsible for interacting with the guanine nucleotide exchange factor (GEF) domain of RalGDS. Immunofluorescence microscopy revealed that RalGDS can be recruited to the late endosomal compartments by RILP. Further investigations indicated that the overexpression of RILP inhibits the activity of RalA, a downstream target of RalGDS. Our data suggest that RILP suppresses the invasion of breast cancer cells by interacting with RalGDS to inhibit its GEF activity for RalA.

来源: Cell Death&Disease 浏览次数:0

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