@article{7198d637493447749e40d19097891e46,
title = "Targeting interleukin-17 receptor B enhances gemcitabine sensitivity through downregulation of mucins in pancreatic cancer",
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.",
author = "Tsai, {Lung Hung} and Hsu, {Kai Wen} and Chiang, {Cheng Ming} and Yang, {Hsiu Ju} and Liu, {Yu Huei} and Yang, {Shun Fa} and Peng, {Pei Hua} and Cheng, {Wei Chung} and Wu, {Heng Hsiung}",
note = "Funding Information: This work was supported by the “Drug Development Center, China Medical Universit” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan to KW Hsu and HH Wu. This work was supported in part to KW Hsu by Ministry of Science and Technology (MOST 108-2628-B-039-003 and MOST 109-2628-B-039-006). CM Chiang{\textquoteright}s research is supported by NIH Grant 1RO1CA251698-01, CPRIT Grants RP180349 and RP190077, and Welch Foundation grant I-1805. This work was also supported in part to HH Wu by Health and welfare of tobacco products, China Medical University Hospital Cancer Research Center of Excellence (MOHW107-TDU-B-212-114024, Taiwan), and Grant of China Medical University and Ministry of Science and Technology Grants (CMU105-N-02, CMU107-N-03, MOST 105-0210-01-13-01, and MOST106-2320-B-039-052-MY3). Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41598-020-73659-z",
language = "English (US)",
volume = "10",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}