GALNT5 promotes migration and invasion of pancreatic ductal adenocarcinoma cells by activating Erk signaling pathway

• Published in: Biochimica et biophysica acta. General subjects Vol. 1869; no. 3; p. 130769
• Main Authors: Zheng, Yongjia, Lu, Yuxing, Yuan, Fang, Kong, Yun, Mao, Yang, Wang, Shengjun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2025
• Subjects: adenocarcinoma; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; Cell Line, Tumor; Cell Movement; epithelium; Erk pathway; family; GALNT5; Gene Expression Regulation, Neoplastic; genes; glycosylation; Humans; MAP Kinase Signaling System; metastasis; N-Acetylgalactosaminyltransferases - genetics; N-Acetylgalactosaminyltransferases - metabolism; Neoplasm Invasiveness; O-glycosylation; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; PDAC; Polypeptide N-acetylgalactosaminyltransferase; prognosis; sequence analysis; therapeutics; GEO; PAAD; GTEx; GALNT5; DEGs; PDAC; Erk pathway; GALNTs; Pancreatic ductal adenocarcinoma; HPA; O-glycosylation; TCGA
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2025.130769

Aberrant glycosylation has been implicated in promoting the progression and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the contribution of different glycosylation-related genes in PDAC remains to be clarified. In this study, we performed a differential analysis of RNA-Seq data from TCGA and GTEx and found GALNT5 as the most significant upregulated glycosylation-related gene in PDAC. Using publicly available single-cell sequencing data, we further revealed that GALNT5 is predominantly expressed in malignant ductal epithelial cells of PDAC. Correlation analysis indicated that GALNT5 is the essential member of the GALNT family associated with poor prognosis of PDAC. Overexpression of GALNT5 in PANC-1 or MIAPaCa-2 cells with low endogenous GALNT5 enhances migration and invasion. Conversely, knockdown of GALNT5 in AsPC-1 cells with high endogenous GALNT5 inhibits migration and invasion. Mechanistically, we discovered that GALNT5 activates the Erk signaling pathway in PDAC. Our findings suggest GALNT5 is a potential therapeutic target for PDAC. [Display omitted] •GALNT5 is the most significant upregulated glycosylation-related gene in PDAC.•GALNT5 is predominantly expressed in malignant ductal epithelial cells of PDAC.•GALNT5 enhances migration and invasion of PDAC cells in vitro•GALNT5 activates the Erk signaling pathway in PDAC.•GALNT5 is a potential therapeutic target for PDAC.