TRAF2 Cooperates with Focal Adhesion Signaling to Regulate Cancer Cell Susceptibility to Anoikis

Sabrina Daniela da Silva; Bin Xu; Mariana Maschietto; Fabio Albuquerque Marchi; Maisa I. Alkailani; Krikor Bijian; Dingzhang Xiao; Moulay A. Alaoui-Jamali

doi:10.1158/1535-7163.MCT-17-1261

TRAF2 Cooperates with Focal Adhesion Signaling to Regulate Cancer Cell Susceptibility to Anoikis

Sabrina Daniela da Silva, Bin Xu, Mariana Maschietto, Fabio Albuquerque Marchi, Maisa I. Alkailani, Krikor Bijian, Dingzhang Xiao, Moulay A. Alaoui-Jamali

McGill University

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

19 Citations (Scopus)

Abstract

TRAF2, a RING finger adaptor protein, plays an important function in tumor necrosis factor (TNF)-and TNF-like weak inducer of apoptosis (TWEAK)-dependent signaling, in particular during inflammatory and immune responses. We identified a functional interaction of TRAF2 with focal adhesion (FA) signaling involving the focal adhesion kinase (FAK) in the regulation of cell susceptibility to anoikis. Comparison of TRAF2-proficient (TRAF2(+/+)) versus TRAF2-deficient (TRAF2(-/-)), and FAK-proficient (FAK(-/-)) versus FAK-deficient (FAK(-/+)) mouse embryonic fibroblasts and their matched reconstituted cells demonstrated that TRAF2 interacts physically with the N-terminal portion of FAK and colocalizes to cell membrane protrusions. This interaction was found to be critical for promoting resistance to cell anoikis. Similar results were confirmed in the human breast cancer cell line MDA-MB-231, where TRAF2 and FAK downregulation promoted cell susceptibility to anoikis. In human breast cancer tissues, genomic analysis of The Cancer Genome Atlas database revealed coamplification of TRAF2 and FAK in breast cancer tissues with a predictive value for shorter survival, further supporting a potential role of TRAF2-FAK cooperative signaling in cancer progression.

Original language	English
Pages (from-to)	139-146
Number of pages	8
Journal	Molecular Cancer Therapeutics
Volume	18
Issue number	1
DOIs	https://doi.org/10.1158/1535-7163.MCT-17-1261
Publication status	Published - Jan 2019
Externally published	Yes

Keywords

Factor-kappa-b
N-terminal kinase
Tnf
Phosphorylation
Activation
Expression
Resistance
Pathways
Bcl-2
Fak

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10.1158/1535-7163.MCT-17-1261

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title = "TRAF2 Cooperates with Focal Adhesion Signaling to Regulate Cancer Cell Susceptibility to Anoikis",

abstract = "TRAF2, a RING finger adaptor protein, plays an important function in tumor necrosis factor (TNF)-and TNF-like weak inducer of apoptosis (TWEAK)-dependent signaling, in particular during inflammatory and immune responses. We identified a functional interaction of TRAF2 with focal adhesion (FA) signaling involving the focal adhesion kinase (FAK) in the regulation of cell susceptibility to anoikis. Comparison of TRAF2-proficient (TRAF2(+/+)) versus TRAF2-deficient (TRAF2(-/-)), and FAK-proficient (FAK(-/-)) versus FAK-deficient (FAK(-/+)) mouse embryonic fibroblasts and their matched reconstituted cells demonstrated that TRAF2 interacts physically with the N-terminal portion of FAK and colocalizes to cell membrane protrusions. This interaction was found to be critical for promoting resistance to cell anoikis. Similar results were confirmed in the human breast cancer cell line MDA-MB-231, where TRAF2 and FAK downregulation promoted cell susceptibility to anoikis. In human breast cancer tissues, genomic analysis of The Cancer Genome Atlas database revealed coamplification of TRAF2 and FAK in breast cancer tissues with a predictive value for shorter survival, further supporting a potential role of TRAF2-FAK cooperative signaling in cancer progression.",

keywords = "Factor-kappa-b, N-terminal kinase, Tnf, Phosphorylation, Activation, Expression, Resistance, Pathways, Bcl-2, Fak",

author = "{da Silva}, {Sabrina Daniela} and Bin Xu and Mariana Maschietto and Marchi, {Fabio Albuquerque} and Alkailani, {Maisa I.} and Krikor Bijian and Dingzhang Xiao and Alaoui-Jamali, {Moulay A.}",

note = "Publisher Copyright: {\textcopyright} 2018 American Association for Cancer Research.",

year = "2019",

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doi = "10.1158/1535-7163.MCT-17-1261",

language = "English",

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T1 - TRAF2 Cooperates with Focal Adhesion Signaling to Regulate Cancer Cell Susceptibility to Anoikis

AU - da Silva, Sabrina Daniela

AU - Xu, Bin

AU - Maschietto, Mariana

AU - Marchi, Fabio Albuquerque

AU - Alkailani, Maisa I.

AU - Bijian, Krikor

AU - Xiao, Dingzhang

AU - Alaoui-Jamali, Moulay A.

PY - 2019/1

Y1 - 2019/1

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AB - TRAF2, a RING finger adaptor protein, plays an important function in tumor necrosis factor (TNF)-and TNF-like weak inducer of apoptosis (TWEAK)-dependent signaling, in particular during inflammatory and immune responses. We identified a functional interaction of TRAF2 with focal adhesion (FA) signaling involving the focal adhesion kinase (FAK) in the regulation of cell susceptibility to anoikis. Comparison of TRAF2-proficient (TRAF2(+/+)) versus TRAF2-deficient (TRAF2(-/-)), and FAK-proficient (FAK(-/-)) versus FAK-deficient (FAK(-/+)) mouse embryonic fibroblasts and their matched reconstituted cells demonstrated that TRAF2 interacts physically with the N-terminal portion of FAK and colocalizes to cell membrane protrusions. This interaction was found to be critical for promoting resistance to cell anoikis. Similar results were confirmed in the human breast cancer cell line MDA-MB-231, where TRAF2 and FAK downregulation promoted cell susceptibility to anoikis. In human breast cancer tissues, genomic analysis of The Cancer Genome Atlas database revealed coamplification of TRAF2 and FAK in breast cancer tissues with a predictive value for shorter survival, further supporting a potential role of TRAF2-FAK cooperative signaling in cancer progression.

KW - Factor-kappa-b

KW - N-terminal kinase

KW - Tnf

KW - Phosphorylation

KW - Activation

KW - Expression

KW - Resistance

KW - Pathways

KW - Bcl-2

KW - Fak

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SP - 139

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JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

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ER -

TRAF2 Cooperates with Focal Adhesion Signaling to Regulate Cancer Cell Susceptibility to Anoikis

Abstract

Keywords

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