CD99–PTPN12 axis suppresses actin cytoskeleton-mediated dimerization of epidermal growth factor receptor

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

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Article number2895
Pages (from-to)1-24
Number of pages24
JournalCancers
Volume12
Issue number10
DOIs
Publication statusPublished - 2020 Oct

Bibliographical note

Funding Information:
Funding: This work was supported by the Basic science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A3B07043170) and by the 2017 Research Grant from Kangwon National University (No. 520170543).

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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