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CUB-domain containing protein 1 represses the epithelial phenotype of pancreatic cancer cells
Authors:Shin Miura  Shin Hamada  Atsushi Masamune  Kennichi Satoh  Tooru Shimosegawa
Affiliation:1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aobaku, Sendai city, Miyagi 980-8574, Japan;2. Division of Cancer stem cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Shiote, Medeshima, Natori city, Miyagi 981-1293, Japan
Abstract:The prognosis of pancreatic cancer is dismal due to the frequent metastasis and invasion to surrounding organs. Numerous molecules are involved in the malignant behavior of pancreatic cancer cells, but the entire process remains unclear. Several reports have suggested that CUB-domain containing protein-1 (CDCP1) is highly expressed in pancreatic cancer, but its impact on the invasive growth and the upstream regulator remain elusive. To clarify the role of CDCP1 in pancreatic cancer, we here examined the effects of CDCP1 knockdown on the cell behaviors of pancreatic cancer cells. Knockdown of CDCP1 expression in Panc-1 resulted in reduced cellular migration accompanied by the increased expression of E-cadherin and decreased expression of N-cadherin. Knockdown of CDCP1 attenuated the spheroid formation and resistance against gemcitabine, which are some of the cancer stem cell-related phenotypes. Bone morphogenetic protein 4 (BMP4) was found to induce CDCP1 expression via the extracellular signal regulated kinase pathway, suggesting that CDCP1 has a substantial role in the BMP4-induced epithelial-mesenchymal transition. These results indicate that CDCP1 represses the epithelial phenotype of pancreatic cancer cells.
Keywords:BMP4, bone morphogenetic protein 4   BSA, bovine serum albumin   CDCP1, CUB-domain containing protein 1   CSC, cancer stem cell   DMEM, Dulbecco's modified Eagle's medium   DMSO, dimethylsulfoxide   EGF, epidermal growth factor   EMT, epithelial-mesenchymal transition   ERK, extracellular signal-regulated kinase   FBS, fetal bovine serum   FGF, fibroblast growth factor   GAPDH, glyceraldehyde-3-phosphate dehydrogenase   HGF, hepatocyte growth factor   IL-6, interleukin-6   MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide   PBS, phosphate-buffered saline   PKC, protein kinase c   TGF-β, transforming growth factor-β
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