Temozolomide Induces Endocytosis of EGFRvIII via p38-Mediated Non-canonical Phosphorylation in Glioblastoma Cells

Autor:	Ratna Dini Haryuni, Jun-ichiro Takahashi, Satoru Yokoyama, Yue Zhou, Hiroaki Sakurai, Iimi Onuma, Tomohiro Tanaka
Rok vydání:	2021
Předmět:	Pharmacology Temozolomide biology Chemistry Endosome media_common.quotation_subject Endocytic cycle Pharmaceutical Science General Medicine Endocytosis Gefitinib medicine Cancer research biology.protein Phosphorylation Epidermal growth factor receptor Internalization medicine.drug media_common
Zdroj:	Biological and Pharmaceutical Bulletin. 44:1681-1687
ISSN:	1347-5215 0918-6158
DOI:	10.1248/bpb.b21-00371
Popis:	The ligand-induced internalization of epidermal growth factor receptor (EGFR) is generally considered to attenuate downstream signaling via its endosomal degradation. However, the endocytosis of an oncogenic EGFR variant III (EGFRvIII) is impaired, which leads to persistent signaling from the cell surface, thereby promoting the proliferation and survival of glioblastoma multiforme (GBM) cells. Cellular stress triggers the non-canonical endocytosis-recycling of EGFR by p38-mediated phosphorylation. In the present study, we used temozolomide (TMZ), the standard chemotherapeutic agent for the treatment of GBM patients, to examine whether EGFRvIII is controlled by a non-canonical mechanism. TMZ triggered the endocytic trafficking of serine phosphorylated EGFRvIII. Moreover, phosphorylation and endocytosis were abrogated by the selective p38 inhibitor SB203580, but not gefitinib, indicating that EGFRvIII is recruited to p38-mediated non-canonical endocytosis. The combination of TMZ and SB203580 also showed potential inhibitory effects on the proliferation and motility of glioblastoma cells.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::1e81637fb62109e40a9b016bc22a62e9 https://doi.org/10.1248/bpb.b21-00371 Zobrazit plný text záznamu