Abstract A42: The stem cell signal Musashi is required for pancreatic cancer progression and therapy resistance

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-12, Vol.76 (24_Supplement), p.A42-A42
• Main Authors: Lytle, Nikki K., Fox, Raymond G., Jaquish, Dawn V., Pham, Nhat-Long, Frederick, Park D., Lowy, Andrew M., Reya, Tannishtha
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.PANCA16-A42

Pancreatic cancer is the 4th leading cause of cancer-related deaths in the United States due to advanced stage at diagnosis and poor response to current therapies. There is an urgent need to identify factors that contribute to tumor progression and drug resistance in order to develop novel, more effective therapeutic strategies. Here we show that the RNA binding protein Musashi2 (Msi2) is critically important for pancreatic tumorigenesis: genetic deletion of Msi2 slowed progression of premalignant lesions to adenocarcinoma in the KPf/fC mouse model of pancreatic cancer and led to a profound increase in overall survival. To better understand how Msi2 contributes to tumor progression, we developed a Msi2 reporter mouse and crossed it into the KPf/fC model. We found that Msi2-reporter positive tumor cells are preferentially able to propagate adenocarcinoma growth, and are highly enriched among circulating tumor cells. Importantly, our studies reveal that tumor cells expressing Msi2 are exceptionally resistant to chemotherapy and radiation. Collectively, these studies identify Msi2 as a central regulator of pancreatic cancer and raise the possibility that targeting Msi could be a new approach for the treatment of pancreatic cancer. Citation Format: Nikki K. Lytle, Raymond G. Fox, Dawn V. Jaquish, Nhat-Long Pham, Park D. Frederick, Andrew M. Lowy, Tannishtha Reya.{Authors}. The stem cell signal Musashi is required for pancreatic cancer progression and therapy resistance. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A42.