Silencing of TAZ inhibits the motility of hepatocellular carcinoma cells through autophagy induction

• Main Authors: Zhou W, Weng J, Wu K, Xu X, Wang H, Zhang J, Zhao C, Yang J, Zhang Y, Shen W
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-09-01
• Series: Cancer Management and Research
• Subjects: TAZ; Autophagy; migration; invasion; hepatocellular carcinoma
• Online Access: https://www.dovepress.com/silencing-of-taz-inhibits-the-motility-of-hepatocellular-carcinoma-cel-peer-reviewed-article-CMAR

Wei Zhou,1,2,* Jiachun Weng,1,* Keyan Wu,1,2,* Xiao Xu,1,* Hui Wang,1,* Jing Zhang,3,* Chengxue Zhao,1 Jie Yang,1 Yu Zhang,1,4,5 Weigan Shen1,4,5 1Department of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, People’s Republic of China; 2Department of Internal Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China; 3Department of Internal Medicine, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, People’s Republic of China; 4Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, People’s Republic of China; 5Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Zhang; Weigan ShenDepartment of Cell Biology, School of Medicine of Yangzhou University, No. 136 Middle Jiangyang Street, Yangzhou 225009, Jiangsu, People’s Republic of ChinaTel [phone]Fax [phone]Email [e-mail]; [e-mail]: The aim of the present study was to investigate the effect of knockdown and knockout of the transcriptional co-activator with PDZ-binding motif (TAZ) on the migration, invasion and autophagy of the hepatocellular carcinoma (HCC) cell lines, as well as the functional connection between the autophagy and cell migratory processes induced by loss of TAZ in HCC cell lines.Methods: HCC cell lines SMMC-7721 and SK-HEP1 stably knockdown and knockout of TAZ were established by the lentiviral-mediated TAZ knockdown and knockout approaches. Reverse transcription-quantitative real-time polymerase chain reaction and Western blotting were performed to examine the expression of TAZ and indicated genes in downstream pathways in HCC cell lines. Transwell assay and autophagic flux assay were used to evaluate the effect of TAZ knockdown and knockout on the motility and the autophagy of HCC cell lines.Results: We initially found that TAZ exhibited highly abundant and was expressed predominantly in HCC cell lines with different spontaneous metastatic potential. Through performing loss-of-function assays, we demonstrated that both TAZ knockdown and knockout promoted HCC cell autophagy and reduced HCC cell migration, invasion and epithelial-to-mesenchymal transition. In addition, autophagy inhibition in TAZ knockdown and knockout SMMC-7721 and SK-HEP1 cells in the presence of 3-methyladenine or chloroquine partially abrogated the migratory and invasive ability induced by TAZ knockdown and knockout.Conclusion: Our findings indicated that loss of TAZ in HCC cells suppressed cell motility probably via altering the autophagy, suggesting that TAZ emerges as an important target in regulating cell motility and autophagy in HCC cells, and blocking TAZ may be a novel therapeutic strategy against HCC.Keywords: TAZ, autophagy, migration, invasion, hepatocellular carcinoma