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KIF22 coordinates CAR and EGFR dynamics to promote cancer cell proliferation

机译:KIF22坐标汽车和EGFR动力学,以促进癌细胞增殖

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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.
机译:Coxsackeivirus和腺病毒受体(轿车)是一种跨膜受体,其在细胞 - 细胞粘附中起关键作用。在正常上皮细胞中发现轿车在各种人类肿瘤中增加,包括肺癌。我们调查了汽车对癌细胞生长有助于癌细胞生长的潜在机制,发现人肺癌细胞的耗尽降低了锚定无关的生长,表皮生长因子(EGF) - 依赖性增殖和体内肿瘤生长。 EGF通过激活激酶PKC DELTA诱导汽车的磷酸化及其随后的细胞交界处的迁移化。 EGF促进了轿车的结合到色调蛋白KIF22。 KIF22依赖性调节微管动力学导致延迟EGFR内化,增强EGFR信号传导,以及在细胞 - 细胞连接处的汽车动力学的协调。这些数据表明KIF22在膜受体的协调中的作用,并提供了对抗肺肿瘤生长的潜在的新治疗策略。

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  • 来源
    《Science Signaling》 |2018年第515期|共14页
  • 作者单位

    Kings Coll London Randall Div Cell &

    Mol Biophys New Hunts House Guys Campus London SE1 1UL England;

    Kings Coll London Randall Div Cell &

    Mol Biophys New Hunts House Guys Campus London SE1 1UL England;

    Kings Coll London Randall Div Cell &

    Mol Biophys New Hunts House Guys Campus London SE1 1UL England;

    Kings Coll London Div Asthma Allergy &

    Lung Biol 5th Floor Tower Wing Guys Hosp Campus London SE1 1UL England;

    Kings Coll London Randall Div Cell &

    Mol Biophys New Hunts House Guys Campus London SE1 1UL England;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

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