Effect of NELL1 on lung cancer stem‑like cell differentiation.

The cancer stem cell theory recently has received enormous attention in cancer biology. Lung cancer stem‑like cells are a subpopulation of undifferentiated lung tumor cells critical for lung cancer tumorigenesis, metastasis and resistance to therapy and disease relapse. The neural EGFL like 1 (NELL1) is a potent growth factor believed to preferentially target cells committed to the osteochondral lineage; yet, its expression and function in lung cancer are largely unknown. In the present study, we used specific medium to accumulate lung cancer stem‑like cells of 95‑D cells in spheres and obtained these highly expressed CD133 cells through flow cytometric cell sorting of CD133‑stained cells which were termed 95‑D lung cancer stem‑like cells (95‑D LCSCs). These 95‑D LCSCs highly expressed stemness genes CD133, Oct4 and Sox2 determined by western blot analysis and quantitative real‑time polymerase chain reaction (qPCR) analysis. Notably, we found that overexpression of NELL1 significantly reduced colony formation and invasion of 95‑D LCSCs tested by soft agar colony formation and cell invasion assay. In addition, as determined by cell proliferation assay, overexpression of NELL1 increased the chemotherapeutic sensitivity of 95‑D LCSCs to carboplatin and cisplatin. NELL1 also reduced the expression of phospho‑MET (p‑MET), Notch3 and HES1, which suggests that NELL1 may induce 95‑D LCSC differentiation by inhibiting the expression of c‑MET‑Notch signaling. Our results suggest that NELL1 induces lung cancer stem‑like cell differentiation, which provides a new potential therapeutic target for cancer stem cells.