ANKRD17 induces pro-survival signaling pathways that enhance cellular invasion and migration during hepatocellular carcinoma tumorigenesis
Vincent W. Keng,
Shan Su,
Elyse S.T. Chui,
Jeffrey C. To,
Yao-jun Zhang,
Xiao-Xiao Li
Affiliations
Vincent W. Keng
The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, China; Department of Applied Biology and Chemical Technology, State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China; Corresponding author
Shan Su
State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510405, China
Elyse S.T. Chui
Department of Applied Biology and Chemical Technology, State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China
Jeffrey C. To
The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, China; Department of Applied Biology and Chemical Technology, State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Yao-jun Zhang
Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510069, China
Xiao-Xiao Li
The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, China; Research Center for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China; Corresponding author
Summary: Metastasis is the primary cause of high mortality in patients with hepatocellular carcinoma (HCC) . A prior study identified ankyrin repeat domain 17 (Ankrd17) as a key gene linked to HCC metastasis. Through reverse genetics, it was observed that mouse liver tumors overexpressing ANKRD17 exhibited a higher tumor load and increased expression of endothelial-mesenchymal transition (EMT) markers. Similarly, ANKRD17 overexpression in human liver cell lines resulted in an amplified cellular motility and invasion capability, whereas knockdown studies reversed this effect. Abnormal regulation of signaling pathways was linked to increased metastasis and survival in cells overexpressing ANKRD17. Notably, the pro-metastatic discoidin domain receptor tyrosine kinase 1 (DDR1) gene was upregulated in these cells, and its suppression reduced motility and invasion without affecting AKT signaling. Clinically, higher ANKRD17 expression correlated with aggressive HCC progression. These findings suggest that ANKRD17 enhances metastatic progression in HCC by activating pro-metastatic and pro-survival pathways.
