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

• Published in: Nature communications Vol. 8; no. 1; pp. 142 - 17
• Main Authors: Haffner, Michael C., Esopi, David M., Chaux, Alcides, Gürel, Meltem, Ghosh, Susmita, Vaghasia, Ajay M., Tsai, Harrison, Kim, Kunhwa, Castagna, Nicole, Lam, Hong, Hicks, Jessica, Wyhs, Nicolas, Biswal Shinohara, Debika, 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26-07-2017; Nature Portfolio
• Subjects: 631/67/589/466; 631/80/84; Actin Cytoskeleton - metabolism; Actins - genetics; Actins - metabolism; Animals; Cell Line; Cell Line, Tumor; Cell Movement; Crystallins - genetics; Crystallins - metabolism; HEK293 Cells; Humanities and Social Sciences; Humans; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Microscopy, Electron, Transmission; Microscopy, Fluorescence; multidisciplinary; Neoplasm Invasiveness; Neoplasm Micrometastasis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - ultrastructure; Protein Binding; RNA Interference; Science; Science (multidisciplinary); Transplantation, Heterologous
• ISSN: 2041-1723; 2041-1723
• 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 β-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.
Invasion of malignant cells involves changes in cytoskeleton dynamics. Here the authors identify absent in melanoma 1 as an actin binding protein and show that it regulates cytoskeletal remodeling and cell migration in prostate epithelial cells, acting as a metastatic suppressor in cancer cells.