Expression of hepaCAM inhibits bladder cancer cell proliferation via a Wnt/β-catenin-dependent pathwayin vitroandin vivo

Abstract

Keywords: bladder cancer, HepaCAM, T24, Wnt/b-catenin Abbreviations: Ad, adenvirus; HepaCAM, hepatocyte cell adhesion molecule.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 b-catenin serves as a pivotal molecule of Wnt pathway. Then, we explored whether the antiproliferation effect of hepaCAM was associated with Wnt/b-catenin pathway in human bladder cancer cells. The negative correlation between hepaCAM and b-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/b-catenin signaling pathway by interfering nuclear protein levels of b-catenin, leading to down-regulate transcriptional activity of LEF/TCF and its target genes c-Myc and cyclinD1. Mechanistically, we demonstrated that hepaCAM-activated GSK3b led to elevate the phosphorylation of b-catenin, contributing to the aberrant translocation of b-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/b-catenin-dependent signaling pathway in vitro and in vivo.

Suppression of the SDF‑1/CXCR4/β‑catenin axis contributes to bladder cancer cell growth inhibition in�vitro and in�vivo

“…MMP-2 is an enzyme that has been implicated in the malignant progression of BCa (44). Usually, β-catenin, c-myc, and MMP-2 have a synergistic effect on BCa tumorigenesis and progression (39,45). In the present study, the suppression of CXCR4 expression also decreased the protein expression of β-catenin targeting genes (MMP-2 and c-myc).…”

“…Previous studies indicated that β-catenin may be a biomarker for the metastatic progression of BCa patients and that it was associated with poor patient survival (37,38). Wnt/β-catenin signaling has been shown to be frequently involved in various signaling pathways related to cell proliferation and metastasis in BCa (39,40). For example, hepatocyte cell adhesion molecule (hepaCAM) specifically suppressed β-catenin expression during BCa cell proliferation (39).…”

“…Wnt/β-catenin signaling has been shown to be frequently involved in various signaling pathways related to cell proliferation and metastasis in BCa (39,40). For example, hepatocyte cell adhesion molecule (hepaCAM) specifically suppressed β-catenin expression during BCa cell proliferation (39). In addition, long non-coding RNA H19 increased BCa metastasis by activating the Wnt/β-catenin signaling pathway (40).…”

ANLN and TLE2 in Muscle Invasive Bladder Cancer: A Functional and Clinical Evaluation Based on In Silico and In Vitro Data

“…In addition, CTNNB1 is highly expressed in RT4 cells and expressed in lower amounts in ScaBER cells, which is similar to the expression pattern of TLE2. The activation of the Wnt/β-catenin signaling pathway plays an important role in tumorigenesis and development of various cancers including BLCA [30][31][32]. Gain-of-function mutations in CTNNB1 are detected in numerous human cancers [33][34][35]; therefore, it is necessary to explore the role of Wnt/β-catenin regulated genes in BLCA.…”

Emerging roles for multifunctional ion channel auxiliary subunits in cancer

“…Similarly, when expressed in MCF-7 breast cancer cells, GlialCAM increases cell motility and adhesion, decreases proliferation, and induces p53-mediated cellular senescence [ 279 , 283 ]. GlialCAM inhibits proliferation and β-catenin signalling in bladder carcinoma cells [ 284 , 285 ]. Furthermore, in renal carcinoma cells, GlialCAM decreases proliferation, induces cell cycle arrest, and stimulates c-Myc degradation [ 286 ].…”