Expression of large tumour suppressor (LATS) kinases modulates chemotherapy response in advanced non-small cell lung cancer.

BACKGROUND

The Hippo signalling pathway plays an important role in regulating organ size and cell proliferation. Down-regulation of large tumour suppressor (LATS) protein homologs or has been found in lung cancer. and are the core components of the Hippo signalling pathway. and share some conserved structural features and exhibit redundant biological functions. The aim of this study was to dissect the interaction between these two homologs.

METHODS

In lung adenocarcinoma (AD) cells, protein expression of and were determined by western blotting; cell viability and apoptosis were measured by MTT and annexin V staining after treatment with cisplatin; subcellular distributions of proteins were determined by immunofluorescence microscopy; expression was modulated by shRNA-mediated knockdown or ectopic expression in cancer cell lines.

RESULTS

Manipulation of the expression of these two kinases influenced cisplatin response in advanced lung AD cell lines. High -to- ratio in H2023 cells was associated with cisplatin resistance, while low -to- ratio in CL1-0 and CL83 cells was associated with sensitivity to cisplatin. Manipulating the -to- ratio by over-expression in CL1-0 and CL83 rendered them resistant to cisplatin treatment, whereas knockdown in H2023 alleviated the -to- ratio and sensitized cancer cells to cisplatin exposure.

CONCLUSIONS

Our data suggested that the ratio of expression of kinases played a role in the modulation of cisplatin sensitivity in advanced lung AD, and targeting of proteins as a novel therapeutic strategy for lung AD deserves further investigation.