Jinyuan Li1, Qiufang Chen1, Zhendong Deng2, Xiaoting Chen2, Hong Liu3, Ying Tao3, Xiaoyu Wang1, Shaoqiang Lin4, Naihua Liu5. 1. The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, PR China. 2. Clinical Department of Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, PR China. 3. The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, PR China. 4. Clinical Department of Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, PR China; The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, PR China; School of Pharmaceutical Sciences of Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China. Electronic address: sqlin123@163.com. 5. The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, PR China. Electronic address: leisonx@sina.com.
Abstract
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.
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 cancerpatients 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 HPV16infection 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.
Authors: Gabriella Baraks; Robert Tseng; Chun-Hao Pan; Saumya Kasliwal; Cindy V Leiton; Kenneth R Shroyer; Luisa F Escobar-Hoyos Journal: Cancer Res Date: 2022-04-01 Impact factor: 13.312
Authors: Omar S El-Masry; Abeer A Alshwareb; Fatimah H Alnasser; Sukainah G Al Mishaal; Khaldoon M Alsamman Journal: J Taibah Univ Med Sci Date: 2022-03-10