Year: 2020
Type: article
Abstract: cyclin-dependent kinase inhibitor, as well as through its ability to directly bind and block the action of several tyrosine kinase receptors. Our previous studies suggested that the lack of decorin promotes hepatic carcinogenesis in mice. Based on this, we set out to investigate whether excess decorin may protect against the liver metastases of colon carcinoma. We also analyzed the effect of decorin in tissue microarrays of human colon carcinoma liver metastasis and examined whether the tumor cells can directly influence the decorin production of myofibroblasts. In humans, low levels of decorin in the liver facilitated the development of colon carcinoma metastases in proportion with more aggressive phenotypes, indicating a possible antitumor action of the proteoglycan. In vitro, colon carcinoma cells inhibited decorin expression in LX2 hepatic stellate cells. Moreover, liver-targeted decorin delivery in mice effectively attenuated metastasis formation of colon cancer. Overexpressed decorin reduced the activity of multiple receptor tyrosine kinases (RTKs) including the epidermal growth factor receptor (EGFR), an important player in colorectal cancer (CRC) pathogenesis. Downstream of that, we observed weakened signaling of ERK1/2, PLCγ, Akt/mTOR, STAT and c-Jun pathways, while p38 MAPK/MSK/CREB and AMPK were upregulated culminating in enhanced p53 function. In conclusion, decorin may effectively inhibit metastatic tumor formation in the liver.
Source: Biomolecules
DOI: 10.3390/biom10081199
Institutions: Semmelweis University, Solvo Biotechnology (Hungary)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,901
OpenAlex ID: W3062907091