ILEI drives epithelial to mesenchymal transition and metastatic progression in the lung cancer cell line A549

Transforming growth factor beta (TGF-beta) induces epithelial-mesenchymal transition (EMT) accompanied by cellular differentiation and migration. Despite extensive transcriptomic profiling, identification of TGF-beta-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-beta 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-beta activation leads to phosphorylation at serine-43 of PCBP1 by protein kinase B beta/Akt2, inducing its release from the ILEI transcript and translational activation. Modulation of hnRNP E1 expression modification altered TGF-beta-mediated reversal of translational silencing of ILEI transcripts and EMT. Furthermore, ILEI could induce, as well as maintain, CD24(low)CD44(high) subpopulation in A549 cells treated with TGF-beta, which might explain its capability to induce metastatic progression. These results thus validate the existence of an evolutionary conserved TGF-beta-inducible post-transcriptional regulon that controls EMT and subsequent metastatic progression of lung cancer.