Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A

Wei Wang, Honghong Zhang, Sali Liu, Chung Kwon Kim, Yilin Xu, Lisa A. Hurley, Ryo Nishikawa, Motoo Nagane, Bo Hu, Alexander H. Stegh, Shi Yuan Cheng, Chonghui Cheng*

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)8366-8371
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number31
DOIs
StatePublished - Aug 1 2017

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Receptor Protein-Tyrosine Kinases
Protein Isoforms
Lysosomes
Monomeric GTP-Binding Proteins
Endosomes
Glioblastoma

Keywords

  • CD44s
  • EGFR
  • GBM
  • Rab7A
  • Splice isoform

ASJC Scopus subject areas

  • General

Cite this

Wang, Wei ; Zhang, Honghong ; Liu, Sali ; Kim, Chung Kwon ; Xu, Yilin ; Hurley, Lisa A. ; Nishikawa, Ryo ; Nagane, Motoo ; Hu, Bo ; Stegh, Alexander H. ; Cheng, Shi Yuan ; Cheng, Chonghui. / Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 31. pp. 8366-8371.
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Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A. / Wang, Wei; Zhang, Honghong; Liu, Sali; Kim, Chung Kwon; Xu, Yilin; Hurley, Lisa A.; Nishikawa, Ryo; Nagane, Motoo; Hu, Bo; Stegh, Alexander H.; Cheng, Shi Yuan; Cheng, Chonghui.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 31, 01.08.2017, p. 8366-8371.

Research output: Contribution to journalArticle

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T1 - Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A

AU - Wang, Wei

AU - Zhang, Honghong

AU - Liu, Sali

AU - Kim, Chung Kwon

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AU - Nishikawa, Ryo

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AU - Cheng, Chonghui

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