Regulation of FAK Activity by Tetraspan Proteins: Potential Clinical Implications in Cancer.
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that regulates multiple cell signaling pathways in both physiological and pathological conditions. Overexpression and activation of FAK is associated with many advanced stage cancers through promoting cancer cell tumorigenicity and progression as well as by regulating the tumor microenvironment. FAK has multiple binding partners through which FAK exerts its functions including RhoGEF, Src family, talin, cortactin, and paxilin. Over the last few years, it has been proposed that a novel group of four transmembrane proteins can interact with FAK and regulate its activity. These include select tetraspanins such as CD151 and CD9 as well as the GAS3 family members epithelial membrane protein-2 (EMP2) and peripheral myelin protein-22 (PMP22). In this review, we discuss the current knowledge of the interaction between FAK and tetraspan proteins in physiological and pathological conditions, with an emphasis on the potential of tetraspan family members as therapeutic targets in cancer.
Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA.
Yu
Y
Qin
Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
Shabnam
S
Mohandessi
Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA.
Lynn
L
Gordon
Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.|Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA.|Center to Eliminate Cancer Health Disparities, Charles Drew University, Los Angeles, CA.
Madhuri
M
Wadehra
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction; D059470:Tetraspanins / Q000187:drug effects / Q000378:metabolism*
D000970:Antineoplastic Agents; D059470:Tetraspanins; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human