KIF22 coordinates CAR and EGFR dynamics to promote cancer cell proliferation

被引:34
作者
Pike, Rosemary [1 ]
Ortiz-Zapater, Elena [1 ,2 ]
Lumicisi, Brooke [1 ]
Santis, George [2 ]
Parsons, Maddy [1 ]
机构
[1] Kings Coll London, Randall Div Cell & Mol Biophys, New Hunts House,Guys Campus, London SE1 1UL, England
[2] Kings Coll London, Div Asthma Allergy & Lung Biol, 5th Floor Tower Wing,Guys Hosp Campus, London SE1 1UL, England
基金
英国生物技术与生命科学研究理事会;
关键词
COXSACKIE-ADENOVIRUS RECEPTOR; TIGHT JUNCTION; LUNG-CANCER; MICROTUBULE-BINDING; CHROMOKINESIN KID; GROWTH; EXPRESSION; SURVIVAL; PHOSPHORYLATION; DEGRADATION;
D O I
10.1126/scisignal.aaq1060
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The coxsackievirus and adenovirus receptor (CAR) is a transmembrane receptor that plays a key role in cell-cell adhesion. CAR is found in normal epithelial cells and is increased in abundance in various human tumors, including lung carcinomas. We investigated the potential mechanisms by which CAR contributes to cancer cell growth and found that depletion of CAR in human lung cancer cells reduced anchorage-independent growth, epidermal growth factor (EGF)-dependent proliferation, and tumor growth in vivo. EGF induced the phosphorylation of CAR and its subsequent relocalization to cell junctions through the activation of the kinase PKC delta. EGF promoted the binding of CAR to the chromokinesin KIF22. KIF22-dependent regulation of microtubule dynamics led to delayed EGFR internalization, enhanced EGFR signaling, and coordination of CAR dynamics at cell-cell junctions. These data suggest a role for KIF22 in the coordination of membrane receptors and provide potential new therapeutic strategies to combat lung tumor growth.
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页数:14
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