KRT17 confers paclitaxel-induced resistance and migration to cervical cancer cells

被引:30
作者
L, Jinyuan [1 ]
Chen, Qiufang [1 ]
Deng, Zhendong [2 ]
Chen, Xiaoting [2 ]
Liu, Hong [3 ]
Tao, Ying [3 ]
Wang, Xiaoyu [1 ]
Lin, Shaoqiang [2 ,3 ,4 ]
Liu, Naihua [3 ]
机构
[1] Jinan Univ, Affiliated Hosp 1, Guangzhou 510632, Guangdong, Peoples R China
[2] Guangdong Pharmaceut Univ, Clin Dept, Guangdong Metab Dis Res Ctr Integrated Chinese &, Guangzhou 510080, Guangdong, Peoples R China
[3] Guangdong Pharmaceut Univ, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China
[4] Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
KRT17; Migration; Proliferation; Paclitaxel; Cervical cancer; KERATIN; 17; EXPRESSION; CHEMORESISTANCE; MICROTUBULES; FILAMENTS; VIMENTIN; INVASION; PATHWAY; BIOLOGY; LESIONS;
D O I
10.1016/j.lfs.2019.03.065
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
Aim: To understand potential pro-oncological effects of lower dose paclitaxel treatment in cervical cancer cells, we investigated the potential roles of KRT17 on migration and proliferation of cervical cancer cells which might respond to cytoskeletal-based drugs treatments. Materials and methods: We extracted the clinic data of cervical cancer patients from TCGA database to investigate mRNA expression of different keratins. HPV genotypes were identified by reverse transcription PCR. krt17 mRNA and EMT markers were quantified by real-time PCR. krt17 and EMT markers protein were immunoblotted by western blot. Cell viability was detected by CCK8. Cell migration was performed by transwell migration assay. Key findings: Our results showed that HPV16 infection correlated with the expression of KRT17 in cervical cancer cell lines. KRT17 knockdown would decrease Snail2 and elevate E-Cadherin to inhibit migration of Caski cells and SiHa cells. Lower dose of paclitaxel promoted SiHa proliferation, it also significantly promoted the migration of Caski cells. Otherwise, colchicine and higher dose of paclitaxel dose-dependently suppressed the proliferation and migration of Caski cells and SiHa cells. Moreover, KRT17 knockdown significantly facilitated cytoskeletal-based drugs to inhibit migration and induce cytotoxicity in cervical cancer cells. Significance: KRT17 played pivotal oncogenic roles in cell survival, migration and paclitaxel-induced resistance of cervical cancer cells. Thus, KRT17 would serve as a promising target for compromising paclitaxel-induced resistance and metastasis.
引用
收藏
页码:255 / 262
页数:8
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