Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice

Abstract

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin in human colorectal cancer cells, we found that E-cadherin, a protein that regulates cell-cell adhesion, epithelial-mesenchymal transition and metastasis, was almost completely lost in Dcn(-/-) mouse intestine, and loss of decorin and E-cadherin accelerated colon cancer cell growth and invasion in Dcn(-/-) mice. However, increasing decorin expression in colorectal cancer cells attenuated cancer cell malignancy, including inhibition of cancer cell proliferation, promotion of apoptosis and importantly, attenuation of cancer cell migration. All these changes were linked to the regulation of E-cadherin by decorin. Moreover, overexpression of decorin upregulated E-cadherin through increasing of E-cadherin protein stability as E-cadherin messenger RNA and promoter activity were not affected. Co-immunoprecipitation assay showed a physical binding between decorin and E-cadherin proteins. Taken together, our results provide direct evidence that decorin-mediated inhibition of colorectal cancer growth and migration are through the interaction with and stabilization of E-cadherin.

Trichostatin A induces mesenchymal-like morphological change and gene expression but inhibits migration and colony formation in human cancer cells

“…5), which was consistent with previous studies reporting that HDAC6 is required for β-catenin activation in colon cancer cells (20,21). Whether TSA-mediated EMT induction and inhibition, elevation of β-catenin mRNA levels and inhibition of β-catenin protein levels are associated with other signaling pathways, such as the decorin-β-catenin-E-cadherin signaling pathway (22), remains unclear and is currently under investigation.…”

Methylated +58CpG site decreases DCN mRNA expression and enhances TGF-β/Smad signaling in NSCLC cells with high metastatic potential

“…Compelling evidence has shown that DCN contributes to inhibition of tumor growth and metastasis (13,(15)(16)(17)(18)(19)34). Goldoni et al reported that DCN can display an anti-metastatic role in breast cancer (16).…”

“…Goldoni et al reported that DCN can display an anti-metastatic role in breast cancer (16). Bi et al demonstrated that DCN may act as a tumor suppressor gene (15) and mediate inhibition of colorectal cancer growth and migration (13). Among soft tissue tumor patients with recurrent or metastatic lesions, lower levels of DCN were expressed in secondary lesions than those in primary lesions (17).…”

“…DCN-mediated inhibition of colorectal cancer migration is associated with E-cadherin (13,(15)(16)(17)(18)(19)34). Here we examined expression of E-cadherin in 95D expressing low DCN and 95C expressing high DCN, and found that E-cadherin expression was significantly lower in 95D cells (0.25±0.05) than 95C cells (0.73±0.07) (P=0.016) (Fig.…”

“…Decorin (DCN) is a member of the extracellular matrix small leucine-rich proteoglycan family (12) and DCN regulates multiple processes in cancer cells (13,14). Accumulative evidence shows that DCN plays an inhibitory role in tumor growth and metastasis (15)(16)(17)(18)(19).…”