通过稳定 Twist1 来调节细胞增殖和迁移的 p62。
Regulation of cell proliferation and migration by p62 through stabilization of Twist1.
机构信息
Departments of Medicine, Section of Dermatology.
Orthopaedic Surgery and Rehabilitation Medicine, and.
出版信息
Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9241-6. doi: 10.1073/pnas.1322913111. Epub 2014 Jun 9.
Abstract
The selective autophagy substrate p62 serves as a molecular link between autophagy and cancer. Suppression of autophagy causes p62 accumulation and thereby contributes to tumorigenesis. Here we demonstrate that autophagy deficiency promotes cell proliferation and migration through p62-dependent stabilization of the oncogenic transcription factor Twist1. p62 binds to Twist1 and inhibits degradation of Twist1. In mice, p62 up-regulation promotes tumor cell growth and metastasis in a Twist1-dependent manner. Our findings demonstrate that Twist1 is a key downstream effector of p62 in regulation of cell proliferation and migration and suggest that targeting p62-mediated Twist1 stabilization is a promising therapeutic strategy for prevention and treatment of cancer.
摘要
选择性自噬底物 p62 作为自噬和癌症之间的分子联系。自噬的抑制会导致 p62 的积累，从而促进肿瘤发生。在这里，我们证明了自噬缺陷通过 p62 依赖性稳定致癌转录因子 Twist1 促进细胞增殖和迁移。p62 与 Twist1 结合并抑制 Twist1 的降解。在小鼠中，p62 的上调以 Twist1 依赖的方式促进肿瘤细胞的生长和转移。我们的研究结果表明，Twist1 是 p62 调节细胞增殖和迁移的关键下游效应因子，并表明靶向 p62 介导的 Twist1 稳定是预防和治疗癌症的一种有前途的治疗策略。
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