AIM1 is an actin-binding protein that suppresses cell migration and micrometastatic dissemination

作者：Haffner Michael C; Esopi David M; Chaux Alcides; Gurel Meltem; Ghosh Susmita; Vaghasia Ajay M; Tsai Harrison; Kim Kunhwa; Castagna Nicole; Lam Hong; Hicks Jessica; Wyhs Nicolas; Shinohara Debika Biswal; Hurley Paula J; Simons Brian W; Schaeffer Edward M; Lotan Tamara L; Isaacs William B; Netto George J; De Marzo Angelo M; Nelson William G; An Steven S; Yegnasubramanian Srinivasan^*

来源：Nature Communications, 2017, 8(1): 142.

DOI：10.1038/s41467-017-00084-8

A defining hallmark of primary and metastatic cancers is the migration and invasion of malignant cells. These invasive properties involve altered dynamics of the cytoskeleton and one of its major structural components beta-actin. Here we identify AIM1 (absent in melanoma 1) as an actin-binding protein that suppresses pro-invasive properties in benign prostate epithelium. Depletion of AIM1 in prostate epithelial cells increases cytoskeletal remodeling, intracellular traction forces, cell migration and invasion, and anchorage-independent growth. In addition, decreased AIM1 expression results in increased metastatic dissemination in vivo. AIM1 strongly associates with the actin cytoskeleton in prostate epithelial cells in normal tissues, but not in prostate cancers. In addition to a mislocalization of AIM1 from the actin cytoskeleton in invasive cancers, advanced prostate cancers often harbor AIM1 deletion and reduced expression. These findings implicate AIM1 as a key suppressor of invasive phenotypes that becomes dysregulated in primary and metastatic prostate cancer.

• 出版日期2017-7-26