title: PCDH10, a novel p53 transcriptional target in regulating cell migration.
abstract: Cell cycle arrest, senescence and apoptosis are commonly regarded as the major tumor suppression mechanisms of p53. However, accumulating evidence indicates that loss of these canonical functions is not sufficient for tumor formation, highlighting the complexity of p53-mediated tumor suppression. PCDH10 belongs to a proto cadherin protein family and is a potential tumor suppressor protein as the dysregulation of PCDH10 gene frequently existed in multiple human tumors. Here, we found that PCDH10 is a transcriptional target of p53 and that the levels of PCDH10 expression can be induced by wild type p53 but not mutant p53 in a number of human cancer cell lines. Moreover, we identified a p53 consensus binding site located in the PCDH10 promoter region that is responsive to p53 regulation. Although upregulation of PCDH10 has no obvious effect on growth arrest or apoptosis in human cells, PCDH10 exhibits inhibitory roles in cancer cell motility and cell migration. These results suggest an important role of p53 in regulating tumor cell migration through activating PCDH10 expression and support the notion that non-canonical activities of p53 may contribute to its tumor suppressor function in vivo.
authors.affiliation: a Institute for Cancer Genetics and Department of Pathology and Cell Biology; College of Physicians & Surgeons ; Columbia University ; New York , NY USA.
authors.forename: Dingding
authors.initials: D
authors.lastname: Shi
authors.forename: Vundavalli V
authors.initials: VV
authors.lastname: Murty
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
mesh_terms: D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D000091363:Protocadherins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D015820:Cadherins; C438603:PCDH10 protein, human; D000091363:Protocadherins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53
keywords: PCDH10; apoptosis and cell migration; cell cycle arrest; p53; senescence