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 language | English (US) |
|---|---|
| Pages (from-to) | 8366-8371 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 114 |
| Issue number | 31 |
| DOIs | |
| State | Published - Aug 1 2017 |
Funding
We thank Xiaodan Lin for technical assistance. We thank Andrea Calvert for providing GBM cell lines. This research was supported in part by grants from the US NIH [R01 CA182467 (to C.C.) and NS093843, NS095634, and CA158911 (to S.Y.C.)] and the Northwestern University Brain Tumor Institute (to C.C.) and a Brain Cancer Research Award from James S. McDonnell Foundation (to B.H.). S.Y.C. is a Zell Scholar at Northwestern University. C.C. is a Cancer Prevention Research Institute of Texas Scholar in Cancer Research.
Keywords
- CD44s
- EGFR
- GBM
- Rab7A
- Splice isoform
ASJC Scopus subject areas
- General
