Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer
oleh: Yang Zhang, Xiaoyi Chen, Huamin Wang, Shanisha Gordon-Mitchell, Srabani Sahu, Tushar D. Bhagat, Gaurav Choudhary, Srinivas Aluri, Kith Pradhan, Plabani Sahu, Milagros Carbajal, Hui Zhang, Beamon Agarwal, Aditi Shastri, Robert Martell, Daniel Starczynowski, Ulrich Steidl, Anirban Maitra, Amit Verma
| Format: | Article |
|---|---|
| Diterbitkan: | BMC 2022-05-01 |
Deskripsi
Abstract Advanced pancreatic ductal adenocarcinoma (PDAC) is usually an incurable malignancy that needs newer therapeutic targets. Interleukin-1 receptor accessory protein (IL1RAP) is an innate immune mediator that regulates activation of pro-inflammatory and mitogenic signaling pathways. Immunohistochemistry on tissue microarrays demonstrated expression of IL1RAP in majority of human PDAC specimens and in murine pancreatic tumors from K-RasG122D/p53R172H/PDXCre (KPC) mice. Single cell RNA-Seq analysis of human primary pre-neoplastic lesions and adenocarcinoma specimens indicated that overexpression occurs during carcinogenesis. IL1RAP overexpression was associated with worse overall survival. IL1RAP knockdown significantly reduced cell viability, invasiveness, and clonogenic growth in pancreatic cancer cell lines. Inhibition of the downstream interleukin-1 receptor-associated kinase 4 (IRAK4) using two pharmacologic inhibitors, CA-4948 and PF06650833, resulted in reduced growth in pancreatic cancer cell lines and in xenograft models.