ILEI drives epithelial to mesenchymal transition and metastatic progression in the lung cancer cell line A549
- 438 Downloads
Transforming growth factor beta (TGF-β) induces epithelial–mesenchymal transition (EMT) accompanied by cellular differentiation and migration. Despite extensive transcriptomic profiling, identification of TGF-β-inducible, EMT-specific genes during metastatic progression of lung cancer remains elusive. Here, we functionally validate a previously described post-transcriptional pathway by which TGF-β modulates expression of interleukin-like EMT inducer (ILEI), and EMT itself. We show that poly r(C)-binding protein 1 (PCBP1) binds ILEI transcript and repress its translation. TGF-β activation leads to phosphorylation at serine-43 of PCBP1 by protein kinase Bβ/Akt2, inducing its release from the ILEI transcript and translational activation. Modulation of hnRNP E1 expression modification altered TGF-β-mediated reversal of translational silencing of ILEI transcripts and EMT. Furthermore, ILEI could induce, as well as maintain, CD24lowCD44high subpopulation in A549 cells treated with TGF-β, which might explain its capability to induce metastatic progression. These results thus validate the existence of an evolutionary conserved TGF-β-inducible post-transcriptional regulon that controls EMT and subsequent metastatic progression of lung cancer.
KeywordsILEI Lung cancer Metastasis Epithelial–mesenchymal transition Cancer stem cells
Conflicts of interest
- 1.American Cancer Society. Global cancer facts and figures. 2nd ed. 2008. p15. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-027766.pdf. Accessed 10 Sep 2012.
- 2.World Health Organization. Cancer fact sheet. http://www.who.int/mediacentre/factsheets/fs297/en/. Accessed 10 Sep 2012.
- 21.Thomson S, Buck E, Petti F, Griffin G, Brown E, Ramnarine N, et al. Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res. 2005;65:9455–62.PubMedCrossRefGoogle Scholar