title: Expression of hepaCAM inhibits bladder cancer cell proliferation via a Wnt/β-catenin-dependent pathway in vitro and in vivo.
abstract: We previously established that hepatocyte cell adhesion molecule (hepaCAM), a typical structure of immunoglobulin (Ig)-like adhesion molecules, inhibited the proliferation and the progression of cultured human bladder cancer cells. As increasing evidence reveals that aberrant activation of canonical Wnt pathway is involved in the pathogenesis of bladder cancer, and β-catenin serves as a pivotal molecule of Wnt pathway. Then, we explored whether the anti-proliferation effect of hepaCAM was associated with Wnt/β-catenin pathway in human bladder cancer cells. The negative correlation between hepaCAM and β-catenin in transitional cell carcinoma of bladder (TCCB) was found. Follow by, studied the effect of hepaCAM on the key elements of Wnt pathway. Here, Our researches showed that hepaCAM played a central role in modulating the Wnt/β-catenin signaling pathway by interfering nuclear protein levels of β-catenin, leading to down-regulate transcriptional activity of LEF/TCF and its target genes c-Myc and cyclinD1. Mechanistically, we demonstrated that hepaCAM-activated GSK3β led to elevate the phosphorylation of β-catenin, contributing to the aberrant translocation of β-catenin. In addition, Anti-proliferation and associated molecular mechanisms of hepaCAM were demonstrated by using vivo experiment. In conclusion, our reports uncover that expression of hepaCAM suppresses the proliferation of bladder cancer cells through a Wnt/β-catenin-dependent signaling pathway in vitro and in vivo.
authors.affiliation: a Department of Clinical Laboratory ; The First Affiliated Hospital of Chengdu Medical College ; Chengdu , PR China.
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Du
authors.affiliation: b The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education ; Chongqing Medical University ; Chongqing , PR China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Ou
authors.affiliation: c Department of Laboratory Medicine ; Shang qiu Medical College ; Shang qiu , PR China.
authors.forename: Chang-Kun
authors.initials: CK
authors.lastname: Lv
authors.affiliation: b The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education ; Chongqing Medical University ; Chongqing , PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: b The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education ; Chongqing Medical University ; Chongqing , PR China.
authors.forename: Xue-Dong
authors.initials: XD
authors.lastname: Song
authors.affiliation: b The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education ; Chongqing Medical University ; Chongqing , PR China.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Fan
authors.affiliation: d Department of Urology , The First Affiliated Hospital of Chongqing Medical University ; Chongqing , PR China.
authors.forename: Xiao-Hou
authors.initials: XH
authors.lastname: Wu
authors.affiliation: b The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education ; Chongqing Medical University ; Chongqing , PR China.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Luo
mesh_terms: D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C487620:HEPACAM protein, human; D011506:Proteins; D051153:Wnt Proteins; D051176:beta Catenin
keywords: bladder cancer, HepaCAM, T24, Wnt/β-catenin