Evidence of the cross talk between Wnt and Notch signaling pathways in non-small-cell lung cancer (NSCLC): Notch3-siRNA weakens the effect of LiCl on the cell cycle of NSCLC cell lines.

BACKGROUND: Aberrant activations of Wnt and Notch signaling pathways are individually reported to be associated with the pathogenesis of non-small-cell lung cancer (NSCLC). However, the data about the cross talk between the two signaling pathways are still limited. To elucidate potential Wnt/Notch cross talk within NSCLC, we examined the impact of Notch3 activity on LiCl-induced cell cycle changes.

METHODS: The lung cancer cell lines were treated with LiCl, a Wnt activator, in the absence or presence of Notch3-siRNA. Cell cycles and the expression of the regulators of cell cycle, c-MYC, p21 and Skp2 (S phase kinase-associated protein 2) were measured after treatment.

RESULTS: The treatment with LiCl increased the percent of cells at S phase and G phase and the expression of c-MYC and Skp2 and decreased the expression of p21. Moreover, the expression of Notch3 and its down-stream genes, HES-1 and HEYL, was up-regulated by LiCl. Notch3-siRNA weakened the effect of LiCl on the cell cycle and resulted in attenuation of the LiCl-induced increment of c-MYC and Skp2 and the LiCl-induced decrement of p21.

CONCLUSIONS: These data suggest that Notch3 activation cooperatively takes part in the LiCl-induced cell cycle changes, at least partially, associated with c-MYC, Skp2 and p21.