Caveolin-1 promotes pancreatic cancer cell differentiation and restores membranous E-cadherin via suppression of the epithelial-mesenchymal transition

• DOI: 10.4161/cc.10.21.17895
• Publication Date: 2011-11-28T15:16:24Z
• Authors: Ahmed F. Salem; Gloria Bonuccelli; Generoso Bevilacqua; Hwyda Arafat; Richard G. Pestell; Federica Sotgia; Michael P. Lisanti
• Keywords: Caveolin 1

Pancreatic cancer is one of the deadliest cancers due to early rapid metastasis and chemoresistance. Recently, epithelial mesenchymal transition (EMT) was shown play a key role in pathogenesis pancreatic cancer. To understand caveolin-1 (Cav-1) EMT, we over-expressed Cav-1 cell line, Panc 10.05, that does not normally express Cav-1. Here, show expression cells induces an phenotype promotes cell-cell contact, with increased plasma membrane bound E-cadherin beta-catenin. Mechanistically, Snail downregulation decreased activation AKT, MAPK TGF-beta-Smad signaling pathways. In vitro, reduces migration invasion, attenuates doxorubicin-chemoresistance cells. Importantly, vivo studies revealed greatly suppresses tumor formation xenograft model. Most interestingly, Panc/Cav-1 tumors displayed organized nests differentiated were totally absent control tumors. Confirming our vitro results, these showed reexpression beta-catenin at membrane. Thus, provide evidence functions as crucial modulator EMT differentiation