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 J. Hurley; Brian W. Simons; Edward M. Schaeffer; Tamara L. Lotan; William B. Isaacs; George J. Netto; Angelo M. De Marzo; William G. Nelson; Steven S. An; Srinivasan Yegnasubramanian

doi:10.1038/s41467-017-00084-8

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 J. Hurley, Brian W. Simons, Edward M. Schaeffer, Tamara L. Lotan, William B. Isaacs, George J. Netto, Angelo M. De MarzoWilliam G. Nelson, Steven S. An, Srinivasan Yegnasubramanian

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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 language	English (US)
Article number	142
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00084-8
State	Published - Dec 1 2017
Externally published	Yes

All Science Journal Classification (ASJC) codes

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

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10.1038/s41467-017-00084-8

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Haffner, M. C., Esopi, D. M., Chaux, A., Gürel, M., Ghosh, S., Vaghasia, A. M., Tsai, H., Kim, K., Castagna, N., Lam, H., Hicks, J., Wyhs, N., Biswal Shinohara, D., Hurley, P. J., Simons, B. W., Schaeffer, E. M., Lotan, T. L., Isaacs, W. B., Netto, G. J., ... Yegnasubramanian, S. (2017). AIM1 is an actin-binding protein that suppresses cell migration and micrometastatic dissemination. Nature communications, 8(1), [142]. https://doi.org/10.1038/s41467-017-00084-8

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title = "AIM1 is an actin-binding protein that suppresses cell migration and micrometastatic dissemination",

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.",

author = "Haffner, {Michael C.} and Esopi, {David M.} and Alcides Chaux and Meltem G{\"u}rel and Susmita Ghosh and Vaghasia, {Ajay M.} and Harrison Tsai and Kunhwa Kim and Nicole Castagna and Hong Lam and Jessica Hicks and Nicolas Wyhs and {Biswal Shinohara}, Debika and Hurley, {Paula J.} and Simons, {Brian W.} and Schaeffer, {Edward M.} and Lotan, {Tamara L.} and Isaacs, {William B.} and Netto, {George J.} and {De Marzo}, {Angelo M.} and Nelson, {William G.} and An, {Steven S.} and Srinivasan Yegnasubramanian",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41467-017-00084-8",

language = "English (US)",

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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, PJ, Simons, BW, Schaeffer, EM, Lotan, TL, Isaacs, WB, Netto, GJ, De Marzo, AM, Nelson, WG, An, SS & 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

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T1 - AIM1 is an actin-binding protein that suppresses cell migration and micrometastatic dissemination

AU - Haffner, Michael C.

AU - Esopi, David M.

AU - Chaux, Alcides

AU - Gürel, Meltem

AU - Ghosh, Susmita

AU - Vaghasia, Ajay M.

AU - Tsai, Harrison

AU - Kim, Kunhwa

AU - Castagna, Nicole

AU - Lam, Hong

AU - Hicks, Jessica

AU - Wyhs, Nicolas

AU - Biswal Shinohara, Debika

AU - Hurley, Paula J.

AU - Simons, Brian W.

AU - Schaeffer, Edward M.

AU - Lotan, Tamara L.

AU - Isaacs, William B.

AU - Netto, George J.

AU - De Marzo, Angelo M.

AU - Nelson, William G.

AU - An, Steven S.

AU - Yegnasubramanian, Srinivasan

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

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JO - Nature Communications

JF - Nature Communications

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M1 - 142

ER -

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

Abstract

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