Suboj, Babykutty and Priya , Srinivas and S, Asha Nair (2012) Insidious role of nitric oxide in migration/invasion of colon cancer cells by upregulating MMP-2/9 via activation of cGMP-PKGERK signaling pathways. Clinical & experimental metastasis, 29 (5). pp. 471-492. ISSN 1573-7276

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Abstract

Nitric oxide (NO), an uncharged free radical is implicated in various physiological and pathological processes. The present study is an investigation on the effect of NO on proliferation, apoptosis and migration of colon cancer cells. Colon adenocarcinoma cells, WiDr, were used for the in vitro experiments. Tissues from colon adenocarcinoma, adjacent normal and inflammatory tissue and lymph node with metastasis were evaluated for iNOS, MMP-2/9 and Fra-1/Fra-2. NO increases the proliferation of cancer cells and simultaneously prevents apoptosis. Expression of MMP-2/9, RhoB and Rac-1 was enhanced by NO in a time dependent manner. Further, NO increased phosphorylation of ERK1/2 and induced nuclear translocation of Fra-1 and Fra-2. Electrophoretic mobility shift analysis and use of deletion mutant promoter constructs identified role of AP-1 in NO-mediated regulation of MMP-2/9. iNOS, MMP-2/9, Fra-1 and Fra-2 in normal and colon adenocarcinoma tissues were analyzed and it was found that increased expression of these proteins in cancer when compared to normal provides support to our in vitro findings. The study showed that the NO-cGMP-PKG promotes MMP-2/9 expression by activating ERK-1/2 and AP-1. This study reveals the insidious role of NO in imparting tumor aggressiveness.

Item Type:	Article
Uncontrolled Keywords:	Nitric oxideMMP-2/9MigrationColon cancerERK-1/2
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	28 Feb 2017 03:14
Last Modified:	03 Aug 2018 06:51
URI:	http://rgcb.sciencecentral.in/id/eprint/265

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