Abstract 5762: PR55-alpha associated PP2A promotes pancreatic tumorigenesis

• Published in: Cancer research (Chicago, Ill.) Vol. 77; no. 13_Supplement; p. 5762
• Main Authors: Yan, Ying, Hein, Ashley L., Seshacharyulu, Parthasarathy, Rachagani, Satyanarayana, Sheinin, Yuri M., Ouellette, Michel M., Ponnusamy, Moorthy P., Batra, Surinder K.
• Format: Journal Article
• Language: English
• Published: 01.07.2017
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-5762

Abstract PP2A holoenzyme consists of a catalytic subunit, a scaffold subunit, and a regulatory subunit. Loss of function analysis using PP2A catalytic inhibitors or inhibition via tumor viral proteins suggest PP2A as a putative tumor suppressor. However, PP2A has also been shown to facilitate the activation of oncogenic signaling pathways when associated with specific regulatory subunits. In this study, we investigated the possible oncogenic role of PP2A in pancreatic cancer. We found a striking increase in the expression of PR55α, a PP2A regulatory subunit, in pancreatic cancer cells compared to normal pancreatic epithelial cells. Consistently, PR55α expression was markedly elevated in pancreatic ductal adenocarcinoma tissues compared to adjacent normal pancreatic tissues (P<0.0001) and correlated with poor survival of pancreatic cancer patients (P<0.0003). RNAi-mediated depletion of PR55α in pancreatic cancer cells resulted in diminished phosphorylation of both AKT and ERK1/2 and decreased protein levels of β-catenin. Accordingly, pancreatic cancer cells with reduced PR55α expression exhibited significantly impaired properties of transformation, including attenuated cell growth, clonogenicity, mobility, and anchorage-independent growth. Moreover, orthotopic implantation of PR55α-depleted pancreatic cancer cells into nude mice showed a marked reduction in tumorigenicity (P<0.001) and distant metastases. These results suggest that PR55α promotes pancreatic cancer development by sustaining hyperactivity of multiple oncogenic signaling pathways, including AKT, ERK and Wnt. Citation Format: Ying Yan, Ashley L. Hein, Parthasarathy Seshacharyulu, Satyanarayana Rachagani, Yuri M. Sheinin, Michel M. Ouellette, Moorthy P. Ponnusamy, Surinder K. Batra. PR55-alpha associated PP2A promotes pancreatic tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5762. doi:10.1158/1538-7445.AM2017-5762