ILEI drives epithelial to mesenchymal transition and metastatic progression in the lung cancer cell line A549.
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, CD24(low)CD44(high) 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.
Department of Oncology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
Qi
Q
Song
Wei
W
Sheng
Xiaomei
X
Zhang
Shunchang
S
Jiao
Fang
F
Li
D051927:CD24 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016601:RNA-Binding Proteins; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D051927:CD24 Antigen; C497889:CD24 protein, human; D016207:Cytokines; D004268:DNA-Binding Proteins; C514209:FAM3C protein, human; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; C094604:PCBP1 protein, human; D016601:RNA-Binding Proteins; D016212:Transforming Growth Factor beta; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt