TRIM59 promotes gefitinib resistance in EGFR mutant lung adenocarcinoma cells

被引：17

作者：

Cui, Zhilei ^{[1
]}

Liu, Zhen ^{[2
]}

Zeng, Junxiang ^{[3
]}

Zhang, Shulin ^{[4
]}

Chen, Lei ^{[5
]}

Zhang, Guorui ^{[1
]}

Xu, Weiguo ^{[1
]}

Song, Lin ^{[1
]}

Guo, Xuejun ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, XinHua Hosp, Dept Resp Med, Shanghai, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, State Key Lab Microbial Metab, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, XinHua Hosp, Dept Lab Med, Shanghai, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Dept Immunol & Microbiol, Shanghai, Peoples R China

[5] Shanghai Jiao Tong Univ, Sch Med, XinHua Hosp, Dept Pathol, Shanghai, Peoples R China

来源：

LIFE SCIENCES | 2019年 / 224卷

基金：

中国国家自然科学基金;

关键词：

TRIM59; Non-small-cell lung cancer; STAT3; Gefitinib resistance; Phosphorylation; CANCER; STAT3; INHIBITION; ACTIVATION;

D O I：

10.1016/j.lfs.2019.03.041

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Aims: The relationship between TRIM59 and drug resistance is elusive despite of its multiple uncovered roles in human cancers. Here we aimed to characterize the expression status of TRIM59 in gefitinib-resistant EGFR mutant lung adenocarcinoma cells and elucidate its mechanism underlying the drug resistance. Main methods: Gefitinib-resistant cell lines were established by progressive dosage. Relative expression of TRIM59 was determined by both real-time PCR and Western blot. Target gene knockdown was achieved by specific shRNAs. Cell viability was measured by MTT assay. Cell apoptosis was analyzed by flow cytometry with Annexin V/7-AAD double staining. Cell proliferation was determined by clonogenic formation assay. Migration and invasion capacities were detected using transwell chamber assay. Direct interaction between TRIM59 and STAT3 was analyzed by co-immunoprecipitation assay. Key findings: We first observed overexpression of TRIM59 in gefitinib-resistant EGFR mutant lung adenocarcinoma cells. ShRNA-mediated knockdown of TRIM59 significantly inhibited cell viability and stimulated apoptosis. Meanwhile, TRIM59-deficiency suppressed cell migration and invasion. We further identified the interaction between TRIM59 and STAT3. TRIM59-deficiency remarkably impaired the activation of STAT3 signaling. STAT3-specific shRNAs significantly re-sensitized TRIM59-proficient EGFR mutant lung adenocarcinoma cells to gefitinib. Significance: Our data characterized aberrant TRIM59 overexpression in gefitinib-resistance EGFR mutant lung adenocarcinoma cells, and indicated the potential involvement of TRIM59-STAT3 signaling in the occurrence of gefitinib-resistance.

引用

页码：23 / 32

页数：10

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