Back to Search
Start Over
EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation
- Source :
- Cell Death and Disease, Vol 13, Iss 1, Pp 1-11 (2022), Cell Death & Disease
- Publication Year :
- 2022
- Publisher :
- Nature Publishing Group, 2022.
-
Abstract
- Bladder cancer is a highly heterogeneous and aggressive malignancy with a poor prognosis. EGF/EGFR activation causes the detachment of SHC-binding protein 1 (SHCBP1) from SHC adapter protein 1 (SHC1), which subsequently translocates into the nucleus and promotes cancer development via multiple signaling pathways. However, the role of the EGF-SHCBP1 axis in bladder cancer progression remains unexplored. Herein, we report that SHCBP1 is upregulated in bladder cancer tissues and cells, with cytoplasmic or nuclear localization. Released SHCBP1 responds to EGF stimulation by translocating into the nucleus following Ser273 phosphorylation. Depletion of SHCBP1 reduces EGF-induced cell migration and invasiveness of bladder cancer cells. Mechanistically, SHCBP1 binds to RACGAP1 via its N-terminal domain of amino acids 1 ~ 428, and this interaction is enhanced following EGF treatment. Furthermore, SHCBP1 facilitates cell migration by inhibiting RACGAP-mediated GTP-RAC1 inactivation, whose activity is indispensable for cell movement. Collectively, we demonstrate that the EGF-SHCBP1-RACGAP1-RAC1 axis acts as a novel regulatory mechanism of bladder cancer progression, which offers a new clinical therapeutic strategy to combat bladder cancer.
- Subjects :
- rac1 GTP-Binding Protein
Cancer Research
Src Homology 2 Domain-Containing, Transforming Protein 1
Immunology
Active Transport, Cell Nucleus
Article
Cellular and Molecular Neuroscience
RHO signalling
Cell Movement
Cell Line, Tumor
Humans
Cell Proliferation
Cell Nucleus
Epidermal Growth Factor
QH573-671
Hydrolysis
GTPase-Activating Proteins
Bladder cancer
Cell Biology
Shc Signaling Adaptor Proteins
Urinary Bladder Neoplasms
Disease Progression
Cytology
hormones, hormone substitutes, and hormone antagonists
Protein Binding
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 13
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell Death and Disease
- Accession number :
- edsair.doi.dedup.....1a6a069ce79739deb3cdc78168e7c777