Expression of large tumour suppressor (LATS) kinases modulates chemotherapy response in advanced non-small cell lung cancer
Journal
Translational Lung Cancer Research
Journal Volume
9
Journal Issue
2
Pages
294-305
Date Issued
2020
Author(s)
Abstract
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 LATS1 or LATS2 has been found in lung cancer. LATS1 and LATS2 are the core components of the Hippo signalling pathway. LATS1 and LATS2 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 LATS1 and LATS2 were determined by western blotting; cell viability and apoptosis were measured by MTT and annexin V staining after treatment with cisplatin; subcellular distributions of LATS proteins were determined by immunofluorescence microscopy; LATS2 expression was modulated by shRNA-mediated knockdown or ectopic expression in cancer cell lines. Results: Manipulation of the expression of these two LATS kinases influenced cisplatin response in advanced lung AD cell lines. High LATS2-to-LATS1 ratio in H2023 cells was associated with cisplatin resistance, while low LATS2-to-LATS1 ratio in CL1-0 and CL83 cells was associated with sensitivity to cisplatin. Manipulating the LATS2-to-LATS1 ratio by LATS2 over-expression in CL1-0 and CL83 rendered them resistant to cisplatin treatment, whereas LATS2 knockdown in H2023 alleviated the LATS2-to-LATS1 ratio and sensitized cancer cells to cisplatin exposure. Conclusions: Our data suggested that the ratio of expression of LATS kinases played a role in the modulation of cisplatin sensitivity in advanced lung AD, and targeting of LATS proteins as a novel therapeutic strategy for lung AD deserves further investigation. ? Translational lung cancer research. All rights reserved.
Subjects
Hippo; Large tumour suppressor (LATS); Lung cancer
SDGs
Other Subjects
cisplatin; large tumor suppressor kinase 1; large tumor suppressor kinase 2; lipocortin 5; protein kinase; unclassified drug; advanced cancer; apoptosis; Article; cancer cell line; cell viability; cellular distribution; ectopic expression; human; human cell; immunofluorescence microscopy; MTT assay; non small cell lung cancer; protein expression; protein protein interaction; Western blotting
Publisher
AME Publishing Company
Type
journal article