title: Caveolin-1 promotes pancreatic cancer cell differentiation and restores membranous E-cadherin via suppression of the epithelial-mesenchymal transition.
abstract: Pancreatic cancer is one of the deadliest cancers due to early rapid metastasis and chemoresistance. Recently, epithelial to mesenchymal transition (EMT) was shown to play a key role in the pathogenesis of pancreatic cancer. To understand the role of caveolin-1 (Cav-1) in EMT, we over-expressed Cav-1 in a pancreatic cancer cell line, Panc 10.05, that does not normally express Cav-1. Here, we show that Cav-1 expression in pancreatic cancer cells induces an epithelial phenotype and promotes cell-cell contact, with increased expression of plasma membrane bound E-cadherin and beta-catenin. Mechanistically, Cav-1 induces Snail downregulation and decreased activation of AKT, MAPK and TGF-beta-Smad signaling pathways. In vitro, Cav-1 expression reduces cell migration and invasion, and attenuates doxorubicin-chemoresistance of pancreatic cancer cells. Importantly, in vivo studies revealed that Cav-1 expression greatly suppresses tumor formation in a xenograft model. Most interestingly, Panc/Cav-1 tumors displayed organized nests of differentiated cells that were totally absent in control tumors. Confirming our in vitro results, these nests of differentiated cells showed reexpression of E-cadherin and beta-catenin at the cell membrane. Thus, we provide evidence that Cav-1 functions as a crucial modulator of EMT and cell differentiation in pancreatic cancer.
authors: Department of Stem Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors: Ahmed F
authors: AF
authors: Salem
authors: Gloria
authors: G
authors: Bonuccelli
authors: Generoso
authors: G
authors: Bevilacqua
authors: Hwyda
authors: H
authors: Arafat
authors: Richard G
authors: RG
authors: Pestell
authors: Federica
authors: F
authors: Sotgia
authors: Michael P
authors: MP
authors: Lisanti
mesh_terms: D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D051242:Caveolin 1; D051176:beta Catenin