Weiling Xu1,2, Fangchao Gong3, Ting Zhang4, Baorong Chi5, Jingyu Wang6. 1. Department of Hepatobiliary and Pancreatic Medical, The First Hospital of Jilin University, Changchun, 130021, China. 2. Department of Radiology, The First Hospital of Jilin University, Changchun, 130021, China. 3. Department of General Surgery, The First Hospital of Jilin University, Changchun, 130021, China. 4. Department of Ultrasound Room of Hepatobiliary and Pancreatic Medical, The First Hospital of Jilin University, Changchun, 130021, China. 5. Department of Hepatobiliary and Pancreatic Medical, The First Hospital of Jilin University, Changchun, 130021, China. baorong_chi@126.com. 6. Department of Radiology, The First Hospital of Jilin University, Changchun, 130021, China. Wangran306@sohu.com.
Abstract
OBJECTIVES: To investigate the roles of Dead end 1 (Dnd1) in modulating cancer stem cell-related traits of hepatocellular carcinoma (HCC). RESULTS: Dead end (Dnd1) inhibited spheroid formation, suppressed the expression of stemness-related genes, and increased sensitivity to sorafenib in HCC cells. Mechanistically, Dnd1 could bind to 3'-UTR of LATS2, the key kinase of Hippo pathway, thus elevating LATS2 mRNA stability and its expression, subsequently leading to phosphorylation of YAP and its cytoplasmic retention. As a result, epithelial-mesenchymal transition (EMT) was weakened and therefore the generation of HCC stem cell properties was suppressed. CONCLUSIONS: Dnd1 functions as a tumor suppressor by prohibiting CSC-like characteristics via activating Hippo pathway in HCC cells. Dnd1 could thus be a novel therapeutic target for HCC patients.
OBJECTIVES: To investigate the roles of Dead end 1 (Dnd1) in modulating cancer stem cell-related traits of hepatocellular carcinoma (HCC). RESULTS: Dead end (Dnd1) inhibited spheroid formation, suppressed the expression of stemness-related genes, and increased sensitivity to sorafenib in HCC cells. Mechanistically, Dnd1 could bind to 3'-UTR of LATS2, the key kinase of Hippo pathway, thus elevating LATS2 mRNA stability and its expression, subsequently leading to phosphorylation of YAP and its cytoplasmic retention. As a result, epithelial-mesenchymal transition (EMT) was weakened and therefore the generation of HCC stem cell properties was suppressed. CONCLUSIONS:Dnd1 functions as a tumor suppressor by prohibiting CSC-like characteristics via activating Hippo pathway in HCC cells. Dnd1 could thus be a novel therapeutic target for HCC patients.
Entities:
Keywords:
Cancer stem cell; Dnd1; Hepatocellular carcinoma; Hippo; LATS2