Induction of c-Cbl contributes to anti-cancer effects of HDAC inhibitor in lung cancer

Tzu Tang Wei; Yu Chin Lin; Pei Hua Lin; Jin Yuan Shih; Chia Wei Chou; Wei Jan Huang; Yu Chih Yang; Pei Wen Hsiao; Ching Chow Chen

doi:10.18632/oncotarget.3489

Induction of c-Cbl contributes to anti-cancer effects of HDAC inhibitor in lung cancer

Tzu Tang Wei, Yu Chin Lin, Pei Hua Lin, Jin Yuan Shih, Chia Wei Chou, Wei Jan Huang, Yu Chih Yang, Pei Wen Hsiao, Ching Chow Chen

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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.

Original language	English
Pages (from-to)	12481-12492
Number of pages	12
Journal	Oncotarget
Volume	6
Issue number	14
DOIs	https://doi.org/10.18632/oncotarget.3489
Publication status	Published - 2015

Keywords

C-Cbl
EGFR
HDAC inhibitors
Lung cancer

ASJC Scopus subject areas

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.3489

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title = "Induction of c-Cbl contributes to anti-cancer effects of HDAC inhibitor in lung cancer",

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.",

keywords = "C-Cbl, EGFR, HDAC inhibitors, Lung cancer",

author = "Wei, {Tzu Tang} and Lin, {Yu Chin} and Lin, {Pei Hua} and Shih, {Jin Yuan} and Chou, {Chia Wei} and Huang, {Wei Jan} and Yang, {Yu Chih} and Hsiao, {Pei Wen} and Chen, {Ching Chow}",

year = "2015",

doi = "10.18632/oncotarget.3489",

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T1 - Induction of c-Cbl contributes to anti-cancer effects of HDAC inhibitor in lung cancer

AU - Wei, Tzu Tang

AU - Lin, Yu Chin

AU - Lin, Pei Hua

AU - Shih, Jin Yuan

AU - Chou, Chia Wei

AU - Huang, Wei Jan

AU - Yang, Yu Chih

AU - Hsiao, Pei Wen

AU - Chen, Ching Chow

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - C-Cbl

KW - EGFR

KW - HDAC inhibitors

KW - Lung cancer

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ER -

Induction of c-Cbl contributes to anti-cancer effects of HDAC inhibitor in lung cancer

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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