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CD99–PTPN12 Axis Suppresses Actin Cytoskeleton-Mediated Dimerization of Epidermal Growth Factor Receptor.
- Source :
- Cancers; Oct2020, Vol. 12 Issue 10, p2895, 1p
- Publication Year :
- 2020
-
Abstract
- Simple Summary: The epidermal growth factor receptor (EGFR) is activated through growth factor-dependent dimerization accompanied by functional reorganization of the actin cytoskeleton. Lee et al. demonstrate that CD99 activation by agonist ligands inhibits epidermal growth factor (EGF)-induced EGFR dimerization through impairment of cytoskeletal reorganization by protein tyrosine phosphatase non-receptor type 12 (PTPN12)-dependent c-Src/focal adhesion kinase (FAK) inactivation, thereby suppressing breast cancer growth. The epidermal growth factor receptor (EGFR), a member of ErbB receptor tyrosine kinase (RTK) family, is activated through growth factor-induced reorganization of the actin cytoskeleton and subsequent dimerization. We herein explored the molecular mechanism underlying the suppression of ligand-induced EGFR dimerization by CD99 agonists and its relevance to tumor growth in vivo. Epidermal growth factor (EGF) activated the formation of c-Src/focal adhesion kinase (FAK)-mediated intracellular complex and subsequently induced RhoA-and Rac1-mediated actin remodeling, resulting in EGFR dimerization and endocytosis. In contrast, CD99 agonist facilitated FAK dephosphorylation through the HRAS/ERK/PTPN12 signaling pathway, leading to inhibition of actin cytoskeletal reorganization via inactivation of the RhoA and Rac1 signaling pathways. Moreover, CD99 agonist significantly suppressed tumor growth in a BALB/c mouse model injected with MDA-MB-231 human breast cancer cells. Taken together, these results indicate that CD99-derived agonist ligand inhibits epidermal growth factor (EGF)-induced EGFR dimerization through impairment of cytoskeletal reorganization by PTPN12-dependent c-Src/FAK inactivation, thereby suppressing breast cancer growth. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 12
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Cancers
- Publication Type :
- Academic Journal
- Accession number :
- 146748670
- Full Text :
- https://doi.org/10.3390/cancers12102895