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Cancer Res:复旦大学管坤良研究组发表结肠癌发生发展调控机制研究进展

2017-05-10 佚名 生物帮

2017年5月1日,国际著名肿瘤学杂志《Cancer Research》上在线发表了复旦大学生物医学研究院分子与细胞生物学实验室管坤良研究组发表的一篇科研论文,论文题为《内皮素通过激活YAP/TAZ信号促进结直肠癌发生》(“Endothelin promotes colorectal tumorigenesis by activating YAP/TAZ”),研究报道了调节血管收缩的细胞因子内皮素

2017年5月1日,国际著名肿瘤学杂志《Cancer Research》上在线发表了复旦大学生物医学研究院分子与细胞生物学实验室管坤良研究组发表的一篇科研论文,论文题为《内皮素通过激活YAP/TAZ信号促进结直肠癌发生》(“Endothelin promotes colorectal tumorigenesis by activating YAP/TAZ”),研究报道了调节血管收缩的细胞因子内皮素通过下游Hippo-YAP/TAZ信号通路对结肠癌发生发展的重要调控作用。论文第一作者是王珍,通讯作者是实验室教授管坤良、袁海心和熊跃。

结肠癌是一种结肠组织的恶性肿瘤,结肠癌经常与直肠癌并发因此并称为结直肠癌。结直肠癌是世界上第二类最常见的癌症,导致死亡人数位列癌症种类前三。与正常组织相比,结肠癌病例和细胞中都高表达了内皮素受体ETAR,内皮素与其GPCR家族的内皮素受体组成的信号通路可促进细胞生长、细胞存活和细胞迁移等过程,进而诱导肿瘤的发生,然而其细胞内的信号转导通路仍未完全阐明。王珍等的研究工作发现内皮素信号是Hippo通路重要的上游信号,通过内皮素受体和偶联的。

Gαq/11蛋白可以激活YAP/TAZ转录共激活因子,并促进CTGF和CYR61等下游基因的转录表达。这一信号系统对结肠癌细胞的生长、迁移和结肠癌肿瘤的异体移植生长具有重要的促进作用。

该研究工作阐明了Hippo-YAP/TAZ信号通路在介导内皮素信号中的重要作用,以及内皮素受体激活与结肠癌发生的分子机制,为结肠癌的治疗提供了潜在的新的诊断和治疗靶点,也为Hippo信号通路分子抑制剂的研究奠定了应用基础。



原始出处:

Wang Z, Liu P, Zhou X, et al. Endothelin Promotes Colorectal Tumorigenesis by Activating YAP/TAZ. Cancer Res. 2017 May 1.

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