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CD99-PTPN12 Axis Suppresses Actin Cytoskeleton-Mediated Dimerization of Epidermal Growth Factor Receptor

Authors
 Kyoung-Jin Lee  ;  Yuri Kim  ;  Min Seo Kim  ;  Hyun-Mi Ju  ;  Boyoung Choi  ;  Hansoo Lee  ;  Dooil Jeoung  ;  Ki-Won Moon  ;  Dongmin Kang  ;  Jiwon Choi  ;  Jong In Yook  ;  Jang-Hee Hahn 
Citation
 CANCERS, Vol.12(10) : 2895, 2020-10 
Journal Title
CANCERS
Issue Date
2020-10
Keywords
CD99 agonist ; EGFR dimerization ; FAK dephosphorylation ; PTPN12 ; Rac1 ; RhoA ; actin cytoskeletal reorganization ; breast cancer ; endocytosis ; tripeptide
Abstract
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.
Files in This Item:
T999202095.pdf Download
DOI
10.3390/cancers12102895
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Choi, Jiwon(최지원)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184910
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