Abstract B27: Morphological changes, cadherin switching, and growth suppression in pancreatic cancer by GALNT6 knockdown

Abstract Pancreatic Cancer has one of the lowest rates of survival among other cancers. Although molecular targeted therapy has been widely applied for many types of cancer, no effective treatment has been developed for the patients of pancreatic cancer. We previously suggested that GALNT6 (polypeptide N-acetylgalactosaminyltransferase 6) is a promising molecular target in breast cancer by O-type glycosylation of Mucin1. Interestingly, GALNT6 is also up-regulated in pancreatic cancer where Mucin proteins are intensively O-glycosylated, indicating a critical role of GALNT6 in pancreatic cancer. In this study we found that knockdown of GALNT6 using siRNAs decreased Muc4 protein as well as transcription level in pancreatic cancer cells. The knockdown of GALNT6 also decreased HER2 and ERK, interacting proteins of Mucin 4, accompanied by drastic reduction of pancreatic cancer cell viability. Further analysis revealed that knockdown of GALNT6 led to cell morphologic changes like the mesenchymal to epithelial transition, which was in concordant with the cadherin switching mechanism—increase of E-cadherin meanwhile decrease of P-cadherin level. Taking into considerations of important roles of Mucin 4 in growth, invasion and resistance to gemcitabine, our findings imply that targeting GALNT6 is a very promising therapeutic strategy for the treatment of pancreatic cancer patients who still have very limited treatment modalities Citation Format: Yunus Emre Tarhan, Kato Taigo, Miran Jang, Yusuke Nakamura, Jae-Hyun Park. Morphological changes, cadherin switching, and growth suppression in pancreatic cancer by GALNT6 knockdown. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B27.