KIF22 coordinates CAR and EGFR dynamics to promote cancer cell proliferation

TY - JOUR

T1 - KIF22 coordinates CAR and EGFR dynamics to promote cancer cell proliferation

AU - Pike, Rosemary

AU - Ortiz-Zapater, Elena

AU - Lumicisi, Brooke

AU - Santis, George

AU - Parsons, Maddy

PY - 2018/1/30

Y1 - 2018/1/30

N2 - 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. 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.

AB - 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. 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.

UR - http://www.scopus.com/inward/record.url?scp=85041324715&partnerID=8YFLogxK

U2 - 10.1126/scisignal.aaq1060

DO - 10.1126/scisignal.aaq1060

M3 - Article

AN - SCOPUS:85041324715

SN - 1945-0877

VL - 11

JO - Science Signaling

JF - Science Signaling

IS - 515

M1 - eaaq1060

ER -