PIM1 kinase promotes cell proliferation, metastasis and tumor growth of lung adenocarcinoma by potentiating the c-MET signaling pathway

Abstract

The proto-oncogene PIM1 plays essential roles in proliferation, survival, metastasis and drug resistance in hematopoietic and solid tumors. Although PIM1 has been shown to be associated with lymph node metastasis and poor prognosis in non-small cell lung cancer, its underlying molecular mechanisms in this context are still unclear. Here we show that PIM1 is frequently overexpressed in lung adenocarcinomas, and its expression level is associated with c-MET expression and poor clinical outcome. We further demonstrate that PIM1 may regulate c-MET expression via phosphorylation of eukaryotic translation initiation factor 4B (eIF4B) on S406. Depletion of PIM1 decreased cell proliferation, migration, invasion and colony formation in vitro, as well as reduced tumor growth in vivo. And these effects were partially abrogated by restoring of c-MET expression. Our study implicates a promising therapeutic approach in lung adenocarcinoma patients with PIM1 and c-MET overexpression.

Keywords: Lung adenocarcinoma; PIM1; c-MET; eIF4B.