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cGMP‐dependent protein kinases (PKG‐Iβ and PKG‐II) modulate β‐catenin/TCF pathway in cancer cells
Author(s) -
Sellak Hassan,
Wu Songwei,
Lincoln Thomas M.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1087.9
Subject(s) - phosphorylation , cgmp dependent protein kinase , microbiology and biotechnology , kinase , chemistry , wnt signaling pathway , signal transduction , protein kinase a , serine , catenin , cancer research , biology , cyclin dependent kinase 2
The β‐catenin signaling pathway plays an essential role in the development and in diseases such as cancer. Cyclic GMP‐dependent protein kinase (PKG) has been reported to be implicated in β‐catenin signaling. However, the precisemechanism by which PKG modulates β‐catenin pathway isnot completely understood since most of cancer cells loose endogenous PKG expression. The present study was undertaken to determine the effects of ectopic overexpression of PKG on colon cancercell lines. PKG levelswere manipulated in human colon cancer cells by stable transfectionof full‐length PKGcDNA (PKG‐Iβ, PKG‐II) and β‐catenin levels as well as TCF‐luciferase activities were analyzed. In an electromobility shift assay (EMSA), PKG‐I and PKG‐II expression in SW480 colon cancer cells resulted in an increase of TCF, CREB, Ap1, and NF‐kβ binding but not Ap2 or Oct1. Both PKG isoforms stimulation with 8pCPTcGMP induced phosphorylation of VASP (serine 239 ), GSK3β (serine 9 ), and CREB (serine 133 ), while Sox9 phosphorylation (serine 181 ) was only achieved by activated PKG‐II isoform. The results also show that while the overexpression of PKG did not alter total β‐catenin levels, nuclear β‐catenin was slightly increased. The nuclear β‐catenin was concomitant to an increase of TCF‐luciferase activity and binding in PKG overexpressing cells compared to control. These results show that reintroducing PKG (PKG‐Iβ, PKG‐II) in cancer cells affects β‐catenin/TCF pathway and other signals. We are currently exploring the possible contribution of these changes in cell migration, proliferation, and new vessels formation.