Induction of c-Cbl contributes to anti-cancer effects of HDAC inhibitor in lung cancer
Resource
Oncotarget, 6(14), 12481-12492
Journal
Oncotarget
Pages
12481-12492
Date Issued
2015
Date
2015
Author(s)
Lin, Yu-Chin
Lin, Pei-Hua
Chou, Chia-Wei
Huang, Wei-Jan
Yang, Yu-Chih
Hsiao, Pei-Wen
Abstract
Here we found loss of c-Cbl, an E3 ligase, expression in non-small cell lung cancer (NSCLC) compared with its adjacent normal tissue in patient specimens. HDAC inhibition by WJ or knockdown of HDAC 1, HDAC2, HDAC3 or HDAC6 all induced c-Cbl. Ectopic expression of c-Cbl induced decreased EGFR, inhibited growth in NSCLC cells. Knockdown of EGFR inhibited NSCLC growth. Mutation of EGFR at Y1045 decreased WJ-induced growth inhibition as well as in vivo anti-cancer effect and EGFR degradation mediated by WJ. Time-lapse confocal analysis showed co-localization of c-Cbl and EGFR after WJ treatment. Furthermore, WJ inhibited lung tumor growth through c-Cbl induction in orthotopic and tail vein injected models. C-Cbl up-regulation induced by HDACi is a potential strategy for NSCLC treatment.
Subjects
c-Cbl
EGFR
HDAC inhibitors
lung cancer
SDGs
Other Subjects
Cbl protein; cisplatin; epidermal growth factor receptor; histone deacetylase 1; histone deacetylase 2; histone deacetylase 3; histone deacetylase 5; histone deacetylase inhibitor; transcription factor Sp1; vorinostat; Cbl protein; CBL protein, human; histone deacetylase inhibitor; small interfering RNA; animal experiment; animal model; antineoplastic activity; Article; cancer inhibition; concentration response; controlled study; drug mechanism; drug response; enzyme inhibition; histone acetylation; human; human cell; human tissue; in vitro study; in vivo study; lung cancer cell line; male; mouse; non small cell lung cancer; nonhuman; protein degradation; protein expression; protein induction; protein localization; upregulation; animal; apoptosis; biosynthesis; chromatin immunoprecipitation; confocal microscopy; drug effects; drug screening; fluorescent antibody technique; gene silencing; genetic transfection; immunohistochemistry; lung tumor; metabolism; non small cell lung cancer; nonobese diabetic mouse; pathology; SCID mouse; tumor cell line; Animals; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Chromatin Immunoprecipitation; Fluorescent Antibody Technique; Gene Knockdown Techniques; Histone Deacetylase Inhibitors; Humans; Immunohistochemistry; Lung Neoplasms; Male; Mice; Mice, Inbred NOD; Mice, SCID; Microscopy, Confocal; Proto-Oncogene Proteins c-cbl; RNA, Small Interfering; Transfection; Xenograft Model Antitumor Assays