期刊
SCIENCE SIGNALING
卷 11, 期 515, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aaq1060
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资金
- King's Health Partners, National Institute for Health Research (NIHR) Clinical Research Facility
- NIHR Biomedical Research Centre based at Guy's and St. Thomas' National Health Service Foundation Trust, King's College London
- Biotechnology and Biological Sciences Research Council [BB/M503320/1]
- MRC [MC_PC_14105] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [1521896] Funding Source: researchfish
- Medical Research Council [MC_PC_14105] Funding Source: researchfish
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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