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

Michael C. Haffner, David M. Esopi, Alcides Chaux, Meltem Gürel, Susmita Ghosh, Ajay M. Vaghasia, Harrison Tsai, Kunhwa Kim, Nicole Castagna, Hong Lam, Jessica Hicks, Nicolas Wyhs, Debika Biswal Shinohara, Paula Hurley, Brian W. Simons, Edward M. Schaeffer, Tamara Lotan, William B Isaacs, George J. Netto, Angelo Michael Demarzo & 3 others William G Nelson, Steven An, S Yegnasubramanian

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number142
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Microfilament Proteins
Cell Movement
Actins
Melanoma
cancer
proteins
cells
Prostatic Neoplasms
Prostate
Ports and harbors
Actin Cytoskeleton
suppressors
deletion
phenotype
epithelium
Tissue
harbors
traction
Epithelial Cells
depletion

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

AIM1 is an actin-binding protein that suppresses cell migration and micrometastatic dissemination. / 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; Simons, Brian W.; Schaeffer, Edward M.; Lotan, Tamara; Isaacs, William B; Netto, George J.; Demarzo, Angelo Michael; Nelson, William G; An, Steven; Yegnasubramanian, S.

In: Nature Communications, Vol. 8, No. 1, 142, 01.12.2017.

Research output: Contribution to journalArticle

Haffner, MC, Esopi, DM, Chaux, A, Gürel, M, Ghosh, S, Vaghasia, AM, Tsai, H, Kim, K, Castagna, N, Lam, H, Hicks, J, Wyhs, N, Biswal Shinohara, D, Hurley, P, Simons, BW, Schaeffer, EM, Lotan, T, Isaacs, WB, Netto, GJ, Demarzo, AM, Nelson, WG, An, S & Yegnasubramanian, S 2017, 'AIM1 is an actin-binding protein that suppresses cell migration and micrometastatic dissemination', Nature Communications, vol. 8, no. 1, 142. https://doi.org/10.1038/s41467-017-00084-8
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 ; Simons, Brian W. ; Schaeffer, Edward M. ; Lotan, Tamara ; Isaacs, William B ; Netto, George J. ; Demarzo, Angelo Michael ; Nelson, William G ; An, Steven ; Yegnasubramanian, S. / AIM1 is an actin-binding protein that suppresses cell migration and micrometastatic dissemination. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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