TY - JOUR
T1 - CUB-domain containing protein 1 represses the epithelial phenotype of pancreatic cancer cells
AU - Miura, Shin
AU - Hamada, Shin
AU - Masamune, Atsushi
AU - Satoh, Kennichi
AU - Shimosegawa, Tooru
N1 - Funding Information:
This work was supported by the Grant from the Japan Society for the Promotion of Science ( 23591008 , 24790674 and 23390194 ) and the Research Committee of Intractable Pancreatic Diseases (Principal investigator: Tooru Shimosegawa) provided by the Ministry of Health, Labor and Welfare of Japan.
PY - 2014/2/15
Y1 - 2014/2/15
N2 - 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.
AB - 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.
KW - Bone morphogenetic protein 4
KW - CUB-domain containing protein 1
KW - Epithelial-mesenchymal transition
KW - Extracellular signal-regulated kinase
KW - Transforming growth factor-β
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U2 - 10.1016/j.yexcr.2013.12.019
DO - 10.1016/j.yexcr.2013.12.019
M3 - Article
C2 - 24384474
AN - SCOPUS:84895063541
SN - 0014-4827
VL - 321
SP - 209
EP - 218
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -
