Format

Send to

Choose Destination
Mol Cancer Ther. 2019 Jan;18(1):139-146. doi: 10.1158/1535-7163.MCT-17-1261. Epub 2018 Oct 29.

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

Author information

1
Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine, Oncology, and Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
2
Department of Otolaryngology Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
3
Boldrini Children's Center, Campinas, Brazil.
4
AC Camargo Cancer Center and National Institute of Science and Technology on Oncogenomics (INCITO), São Paulo, Brazil.
5
Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
6
Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine, Oncology, and Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. moulay.alaoui-jamali@mcgill.ca.
#
Contributed equally

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.

PMID:
30373932
DOI:
10.1158/1535-7163.MCT-17-1261
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center