Role of YAP in lung cancer resistance to cisplatin.

ABSTRACT

Yes-associated protein (YAP) serves a critical role in the initiation and progression of a variety of types of cancer via modulating the expression of genes involved in cell proliferation and the downregulation of apoptosis. Recent studies have suggested that YAP is responsible for the development of drug resistance and cancer metastasis and recurrence. However, the association between YAP and chemoresistance in lung cancer, particularly in lung cancer stem cells (LCSCs) remains largely unknown. In the current study, lung cancer cell spheres were established using the A549 cell line, which demonstrated stem cell properties. It was revealed that YAP was overexpressed in lung cancer spheres compared with normal A549 adherent cells and was associated with enhanced cisplatin (CDDP) resistance. Knockdown of YAP effectively sensitized the adherent A549 and tumor spheres to CDDP treatment and resulted in enhanced cell death. These results suggest that YAP serves a critical role in LCSCs drug resistance and YAP targeting could become a promising adjuvant to current the chemotherapy for lung cancer.