Unknown

Dataset Information

0

Suppression of AGR2 in a TGF-?-induced Smad regulatory pathway mediates epithelial-mesenchymal transition.


ABSTRACT: During cancer progression, epithelial cancer cells can be reprogrammed into mesenchymal-like cells with increased migratory potential through the process of epithelial-mesenchymal transition (EMT), representing an essential step of tumor progression towards metastatic state. AGR2 protein was shown to regulate several cancer-associated processes including cellular proliferation, survival and drug resistance.The expression of AGR2 was analyzed in cancer cell lines exposed to TGF-? alone or to combined treatment with TGF-? and the Erk1/2 inhibitor PD98059 or the TGF-? receptor specific inhibitor SB431542. The impact of AGR2 silencing by specific siRNAs or CRISPR/Cas9 technology on EMT was investigated by western blot analysis, quantitative PCR, immunofluorescence analysis, real-time invasion assay and adhesion assay.Induction of EMT was associated with decreased AGR2 along with changes in cellular morphology, actin reorganization, inhibition of E-cadherin and induction of the mesenchymal markers vimentin and N-cadherin in various cancer cell lines. Conversely, induction of AGR2 caused reversion of the mesenchymal phenotype back to the epithelial phenotype and re-acquisition of epithelial markers. Activated Smad and Erk signaling cascades were identified as mutually complementary pathways responsible for TGF-?-mediated inhibition of AGR2.Taken together our results highlight a crucial role for AGR2 in maintaining the epithelial phenotype by preventing the activation of key factors involved in the process of EMT.

SUBMITTER: Sommerova L 

PROVIDER: S-EPMC5557473 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

altmetric image

Publications

Suppression of AGR2 in a TGF-β-induced Smad regulatory pathway mediates epithelial-mesenchymal transition.

Sommerova Lucia L   Ondrouskova Eva E   Vojtesek Borivoj B   Hrstka Roman R  

BMC cancer 20170815 1


<h4>Background</h4>During cancer progression, epithelial cancer cells can be reprogrammed into mesenchymal-like cells with increased migratory potential through the process of epithelial-mesenchymal transition (EMT), representing an essential step of tumor progression towards metastatic state. AGR2 protein was shown to regulate several cancer-associated processes including cellular proliferation, survival and drug resistance.<h4>Methods</h4>The expression of AGR2 was analyzed in cancer cell line  ...[more]