Blocking Oncostatin M receptor abrogates STAT3 mediated integrin signaling and overcomes chemoresistance in ovarian cancer. NPJ Precis Oncol 2024 Jun 05;8(1):127
Date
06/06/2024Pubmed ID
38839865Pubmed Central ID
PMC11153533DOI
10.1038/s41698-024-00593-yScopus ID
2-s2.0-85195471255 (requires institutional sign-in at Scopus site)Abstract
Chemotherapy such as cisplatin is widely used to treat ovarian cancer either before or after surgical debulking. However, cancer relapse due to chemotherapy resistance is a major challenge in the treatment of ovarian cancer. The underlying mechanisms related to chemotherapy resistance remain largely unclear. Therefore, identification of effective therapeutic strategies is urgently needed to overcome therapy resistance. Transcriptome-based analysis, in vitro studies and functional assays identified that cisplatin-resistant ovarian cancer cells express high levels of OSMR compared to cisplatin sensitive cells. Furthermore, OSMR expression associated with a module of integrin family genes and predominantly linked with integrin αV (ITGAV) and integrin β3 (ITGB3) for cisplatin resistance. Using ectopic expression and knockdown approaches, we proved that OSMR directly regulates ITGAV and ITGB3 gene expression through STAT3 activation. Notably, targeting OSMR using anti-OSMR human antibody inhibited the growth and metastasis of ovarian cancer cells and sensitized cisplatin treatment. Taken together, our results underscore the pivotal role of OSMR as a requirement for cisplatin resistance in ovarian cancer. Notably, OSMR fostered the expression of a distinct set of integrin genes, which in turn resulted into a crosstalk between OSMR and integrins for signaling activation that is critical for cisplatin resistance. Therefore, targeting OSMR emerges as a promising and viable strategy to reverse cisplatin-resistance in ovarian cancer.
Author List
Geethadevi A, Ku Z, Tsaih SW, Parashar D, Kadamberi IP, Xiong W, Deng H, George J, Kumar S, Mittal S, Zhang N, Pradeep S, An Z, Chaluvally-Raghavan PAuthors
Pradeep Chaluvally-Raghavan PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinDeepak Parashar PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin
