Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-Cadherin in vitro and in mice
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Date
2012-02Author
Bi, Xiuli
Qian, Zhibin
Yang, George R.
Gou, Yuan
Guzman, Grace
Balla, Andre
Iozzo, Renato V.
Yang, Wancai
Pohl, Nicole M.
Publisher
Oxford University PressMetadata
Show full item recordAbstract
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, p27kip1 and E-Cadherin and an upregulation of β-catenin
signaling (Bi et al. Carcinogenesis, 2008). 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 ECadherin
protein stability as E-Cadherin mRNA 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 is through the interaction with and stabilization of E-Cadherin.