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Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A.

ABSTRACT: CD44 has been postulated as a cell surface coreceptor for augmenting receptor tyrosine kinase (RTK) signaling. However, how exactly CD44 triggers RTK-dependent signaling remained largely unclear. Here we report an unexpected mechanism by which the CD44s splice isoform is internalized into endosomes to attenuate EGFR degradation. We identify a CD44s-interacting small GTPase, Rab7A, and show that CD44s inhibits Rab7A-mediated EGFR trafficking to lysosomes and subsequent degradation. Importantly, CD44s levels correlate with EGFR signature and predict poor prognosis in glioblastomas. Because Rab7A facilitates trafficking of many RTKs to lysosomes, our findings identify CD44s as a Rab7A regulator to attenuate RTK degradation.

SUBMITTER: Wang W

PROVIDER: S-EPMC5547599 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A.

Wang Wei W Wang Wei W Zhang Honghong H Liu Sali S Kim Chung Kwon CK Xu Yilin Y Hurley Lisa A LA Nishikawa Ryo R Nagane Motoo M Hu Bo B Stegh Alexander H AH Cheng Shi-Yuan SY Cheng Chonghui C

Proceedings of the National Academy of Sciences of the United States of America 20170717 31

CD44 has been postulated as a cell surface coreceptor for augmenting receptor tyrosine kinase (RTK) signaling. However, how exactly CD44 triggers RTK-dependent signaling remained largely unclear. Here we report an unexpected mechanism by which the CD44s splice isoform is internalized into endosomes to attenuate EGFR degradation. We identify a CD44s-interacting small GTPase, Rab7A, and show that CD44s inhibits Rab7A-mediated EGFR trafficking to lysosomes and subsequent degradation. Importantly, C ...[more]

PMID: 28716909

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