Targeting interleukin-17 receptor B enhances gemcitabine sensitivity through downregulation of mucins in pancreatic cancer
Year: 2020
Type: article
Abstract: Pancreatic cancer is the fourth leading cause of death worldwide due to its poorest prognoses with a 7% 5-year survival rate. Eighty percent of pancreatic cancer patients relapse after chemotherapy and develop early metastasis and drug resistance. Resistance to nucleoside analog gemcitabine frequently used in first-line therapy is an urgent issue in pancreatic cancer treatment. Expression of mucin (MUC) glycoproteins has been shown to enhance chemoresistance via increased cell stemness. Here we show interlukine-17 receptor B (IL-17RB) expression is positively correlated with MUC1 and MUC4 expression in pancreatic cancer cells and tumor tissue. Moreover, IL-17RB transcriptionally up-regulates expression of MUC1 and MUC4 to enhance cancer stem-like properties and resistance to gemcitabine. These results suggest IL-17RB can be a potential target for pancreatic cancer therapy. Indeed, treatment with IL-17RB-neutralizing antibody has a synergistic effect in combination with gemcitabine for killing pancreatic cancer cells. Altogether, these findings provide feasible applications for IL-17RB-targeting therapy in pancreatic cancer treatment.
Source: Scientific Reports
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,870
Funders: Welch Foundation, Cancer Prevention and Research Institute of Texas, Ministry of Health and Welfare, Academia Sinica, China Medical University Hospital, Ministry of Education, India, Ministry of Science and Technology, Taiwan, China Medical University, China Medical University, Taiwan, National Institutes of Health, National Cancer Institute
Awards: Therapeutics Targeting Cancer-Associated HPV Replication, G1212141090, G2341300199, Investigation of the Molecular Basis for Initiating Il-17b/Il-17rb Signaling in Pancreatic Cancer Cells (Ii), The Role and Regulatory Mechanism of 2′-O-Methyladenosine (Am) Modification of Lncrna Mahac in Hypoxia-Induced Tumor Progression( II ), G3764186972, The Role and Regulatory Mechanism of 2′-O-Methyladenosine (Am) Modification of Lncrna Mahac in Hypoxia-Induced Tumor Progression( I ), Molecular Action of Phospho-BRD4–Targeting Compounds in Breast Cancer, G5788181094, G5807253991, G6616560595, Opposing Functions of BRD4 Isoforms in Breast Cancer
OpenAlex ID: W3094158910