title: Metadherin confers chemoresistance of cervical cancer cells by inducing autophagy and activating ERK/NF-κB pathway.
abstract: Overexpression of metadherin (MTDH) has been reported in many solid tumors and implicated in chemoresistance. This study aimed to examine MTDH expression in cervical cancer tissues and explore its role in chemoresistance of cervical cancer. MTDH expression in cervical cancer biopsies and several cervical cancer cell lines was detected by immunoblotting and immunohistochemisty. MTDH expression level was experimentally modulated in HeLa cells to determine the effects on chemoresistance to cisplatin. The results showed that MTDH expression was higher in tissues from both cervical squamous carcinoma and cervical adenocarcinoma, compared to normal cervical tissues. MTDH expression was not correlated to patient age or cervical cancer grade, although nuclear MTDH expression was correlated with poor differentiation of cervical cancer. In SiHa, HeLa, CasKi, and C33A cells, MTDH expression level was positively correlated with chemoresistance to cisplatin. MTDH increased autophagy in HeLa cells, which was associated with decreased cleavage of Caspase-3 and the activation of EER/NF-κB pathway. In conclusion, MTDH expression is high in cervical cancer, and it contributes to chemoresistance of cervical cancer. MTDH could be utilized as a therapeutic target to overcome chemoresistance of cervical cancer.
authors.affiliation: Department of Microbiology, Immunity and Infection, Pathogenic Biology Key Laboratory, Harbin Medical University, Heilongjiang Province, Harbin, 150081, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Zhang
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Qingmeng
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Liping
authors.initials: L
authors.lastname: Tong
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Chen
authors.forename: Yuting
authors.initials: Y
authors.lastname: Ji
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Shang
authors.forename: Baozhan
authors.initials: B
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Chu
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wei
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D001343:Autophagy; D053148:Caspase 3 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D002584:Cervix Uteri / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D002945:Cisplatin