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Open AccessArticle

The Protective Role of Decorin in Hepatic Metastasis of Colorectal Carcinoma

1
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői Street 26, H-1085 Budapest, Hungary
2
Solvo Biotechnology, H-1117 Budapest, Hungary
3
2nd Department of Pathology, Semmelweis University, H-1091 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(8), 1199; https://doi.org/10.3390/biom10081199
Received: 30 June 2020 / Revised: 7 August 2020 / Accepted: 15 August 2020 / Published: 18 August 2020
Decorin, the prototype member of the small leucine-rich proteoglycan gene family of extracellular matrix (ECM) proteins, acts as a powerful tumor suppressor by inducing the p21Waf1/Cip1 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. View Full-Text
Keywords: decorin; ECM; colorectal carcinoma; RTK; signaling; liver metastasis decorin; ECM; colorectal carcinoma; RTK; signaling; liver metastasis
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MDPI and ACS Style

Reszegi, A.; Horváth, Z.; Karászi, K.; Regős, E.; Postniková, V.; Tátrai, P.; Kiss, A.; Schaff, Z.; Kovalszky, I.; Baghy, K. The Protective Role of Decorin in Hepatic Metastasis of Colorectal Carcinoma. Biomolecules 2020, 10, 1199. https://doi.org/10.3390/biom10081199

AMA Style

Reszegi A, Horváth Z, Karászi K, Regős E, Postniková V, Tátrai P, Kiss A, Schaff Z, Kovalszky I, Baghy K. The Protective Role of Decorin in Hepatic Metastasis of Colorectal Carcinoma. Biomolecules. 2020; 10(8):1199. https://doi.org/10.3390/biom10081199

Chicago/Turabian Style

Reszegi, Andrea; Horváth, Zsolt; Karászi, Katalin; Regős, Eszter; Postniková, Victoria; Tátrai, Péter; Kiss, András; Schaff, Zsuzsa; Kovalszky, Ilona; Baghy, Kornélia. 2020. "The Protective Role of Decorin in Hepatic Metastasis of Colorectal Carcinoma" Biomolecules 10, no. 8: 1199. https://doi.org/10.3390/biom10081199

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