Y-Box Binding Protein-1 Promotes Epithelial-Mesenchymal Transition in Sorafenib-Resistant Hepatocellular Carcinoma Cells

• DOI: 10.3390/ijms22010224
• Publication Date: 2020-12-29T01:03:03Z
• Authors: Li-Zhu Liao; Chih-Ta Chen; Nien-Chen Li; Liang-Chun Lin; Bo-Shih Huang; Ya-Hui Chang; Lu-Ping Chow
• Keywords: 0301 basic medicine; Carcinoma, Hepatocellular; Epithelial-Mesenchymal Transition; epithelial-mesenchymal transition; YB-1; Article; Mice; Phosphoserine; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Biomarkers, Tumor; Animals; Humans; Neoplasm Invasiveness; Pseudopodia; Phosphorylation; Cell Proliferation; drug resistance; Liver Neoplasms; Reproducibility of Results; Sorafenib; Prognosis; hepatocellular carcinoma cell; 3. Good health; Gene Expression Regulation, Neoplastic; Drug Resistance, Neoplasm; sorafenib; S102 phosphorylation; Signal Transduction

Hepatocellular carcinoma is one of the most common cancer types worldwide. In cases advanced-stage disease, sorafenib considered treatment choice. However, resistance to remains a major obstacle for effective clinical application. Based on integrated phosphoproteomic and The Cancer Genome Atlas (TCGA) data, we identified transcription factor, Y-box binding protein-1 (YB-1), with elevated phosphorylation Ser102 in sorafenib-resistant HuH-7R cells. Phosphoinositide-3-kinase (PI3K) protein kinase B (AKT) were activated by sorafenib, which, turn, increased level YB-1. functional analyses, knockdown YB-1 led decreased cell migration invasion vitro. At molecular level, inhibition induced suppression zinc-finger SNAI1 (Snail), twist-related 1 (Twist1), E-box-binding homeobox (Zeb1), matrix metalloproteinase-2 (MMP-2) vimentin levels, implying role epithelial-mesenchymal transition (EMT) process Additionally, contributes morphological alterations resulting from F-actin rearrangement through Cdc42 activation. Mutation analyses revealed that at S102 affects migratory invasive potential Our collective findings suggest promotes effect EGFR/PI3K/AKT pathway, leading significant enhancement hepatocellular (HCC) metastasis. Elucidation specific mechanisms action may aid development strategies suppress metastasis overcome resistance.