title: P-cadherin promotes liver metastasis and is associated with poor prognosis in colon cancer.
abstract: P-cadherin belongs to the family of classic cadherins, which is important for maintaining cellular localization and tissue integrity. Recently, it has become evident that P-cadherin contributes to the oncogenesis of many tumor types, including melanoma, prostate, breast, and colon carcinomas. Although cadherin switching is a crucial step in metastasis, the role of P-cadherin in colon cancer metastasis to the liver is unknown. In this study, we performed gene expression analysis and found that the level of P-cadherin was higher in tissue from liver metastases of colon cancer than in the corresponding primary colon cancer tissues. IHC analysis also showed that P-cadherin expression was significantly higher in liver metastases than in paired primary colorectal cancer tumors. Knockdown of P-cadherin in colon cancer cells inhibited wound healing, proliferation, and colony formation and resulted in developing fewer liver metastatic foci and reducing the tumor burden in vivo. Inhibition of P-cadherin expression also induced the up-regulation of E-cadherin and the down-regulation of β-catenin and its downstream target molecules, including survivin and c-Myc. In summary, these results uncover a novel function of P-cadherin in the regulation of colon cancer metastasis to the liver, suggesting that blocking the activity of P-cadherin or its associated signaling may be a valuable target for the treatment of hepatic metastases of colon carcinomas.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Sun
authors.forename: Hai
authors.initials: H
authors.lastname: Hu
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Jian
authors.initials: J
authors.lastname: Pan
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yang
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Ran
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051176:beta Catenin