Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 31, Pages 8366-8371Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1701289114
Keywords
CD44s; splice isoform; EGFR; Rab7A; GBM
Categories
Funding
- US NIH [R01 CA182467, NS093843, NS095634, CA158911]
- Northwestern University Brain Tumor Institute
- James S. McDonnell Foundation
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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.
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