Small interfering RNA-mediated downregulation of beta-catenin inhibits invasion and migration of colon cancer cells in vitro

Abstract

SummaryBackgroundAbnormal regulation of Wnt/β-catenin signaling and subsequently increased β-catenin expression have been found to be involved in the proliferation and growth of colon cancer cells. Whether the down-regulation of β-catenin in colon cancer may result in compromised invasion and migration in vitro still remains to be determined.Material/MethodsA human colon cancer cell line (LoVo cells) was transfected with small interfering RNA (siRNA) targeting β-catenin. RT-PCR, Western blot assay, flow cytometry, cell adhesion assay, scratch wound assay, and matrigel invasion assay were performed, and the correlation between cell invasion and migration and β-catenin expressions was analyzed.ResultssiRNA-mediated down-regulation of β-catenin elevated the E-cadherin expression but reduced the MMP-7 and CD44v6 expressions, which increased the adhesion between LoVo cells but decreased the adhesion of LoVo cells to fibronectin. Significant inhibition of cell invasion and migration was also observed following RNA interference with β-catenin siRNA.ConclusionssiRNA-mediated downregulation of β-catenin could be valuable for defining gene expression and functional programs downstream of oncogenic β-catenin signals, which, in turn, may be helpful to isolate novel diagnostic markers, and for designing tumor-specific intervention at downstream targets of oncogenic β-catenin.

4,6,4′‐trimethylangelicin shows high anti‐proliferative activity on DU145 cells under both UVA and blue light

“…26 Indeed, nuclear translocation of β-catenin is inhibited by silencing CD44 in several cancer cells, including PCa cell lines. 27 Overall, our results indicate, for the first time, that TMA can be activated by BL, although at higher concentrations than UVA light, decreasing the risk of mutagenic lesions on treated cells. Thus, the toxicity of both light and compound itself on neighbouring healthy cells could be overcome with a BL-TMA-targeted treatment in the site of the cancer lesions.…”

“…CD44 is not only a Wnt target gene but also a positive regulator of Wnt pathway through interaction with LRP6 . Indeed, nuclear translocation of β‐catenin is inhibited by silencing CD44 in several cancer cells, including PCa cell lines …”

Molecular targets and pathways involved in liver metastasis of colorectal cancer

“…Retrospectively, it is agreed that the biology of MMP's is far more complex than anticipated. It turned out that they exert pro-and anti-tumoral functions via their indirect signaling function due to cleavage of a whole cascade of signaling molecules in the context of the protease web [36][37][38][39]. This late insight in mind, it is not surprising anymore that broad spectrum MMPI's can exhibit unforeseen effects including the promotion of liver metastasis formation in different tumor models [40].…”

β-Catenin Expression Regulates Cell Migration of Human Colonic Adenocarcinoma Cells Through Gelsolin

“…By contrast, other studies indicated the opposite role of βcatenin in colonic cancer metastasis. Han et al showed that siRNA-mediated down-regulation of β-catenin resulted in suppression of invasiveness and migration of the colonic cancer cell line LoVo, which was accompanied by increased cellular homotypic adhesion (36). It is possible that the discrepancies in results were caused by pathomorphological differences of these two cell lines.…”