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<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 lines exposed to TGF-β alone or to combined treatment with TGF-β and the Erk1/2 inhibitor PD98059 or the TGF-β 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.<h4>Results</h4>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-β-mediated inhibition of AGR2.<h4>Conclusion</h4>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.

Original publication

DOI

10.1186/s12885-017-3537-5

Type

Journal article

Journal

BMC cancer

Publication Date

15/08/2017

Volume

17

Addresses

RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53, Brno, Czech Republic.

Keywords

Cell Line, Tumor, Humans, Vimentin, Transforming Growth Factor beta, Proteins, Cadherins, Cell Adhesion, Signal Transduction, Cell Movement, Gene Expression Regulation, Neoplastic, Smad Proteins, Gene Knockdown Techniques, Epithelial-Mesenchymal Transition