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

TitleExpression of large tumour suppressor (LATS) kinases modulates chemotherapy response in advanced non-small cell lung cancer
Authors
KeywordsHippo
large tumour suppressor (LATS)
lung cancer
Issue Date2020
PublisherAME Publishing Company. The Journal's web site is located at http://www.tlcr.org/
Citation
Translational Lung Cancer Research, 2020, v. 9 n. 2, p. 294-305 How to Cite?
AbstractBackground: 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.
Persistent Identifierhttp://hdl.handle.net/10722/287376
ISSN
2020 Impact Factor: 6.498
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLuo, SY-
dc.contributor.authorKwok, HH-
dc.contributor.authorYang, PC-
dc.contributor.authorIp, MSM-
dc.contributor.authorMinna, JD-
dc.contributor.authorLam, DCL-
dc.date.accessioned2020-09-22T03:00:07Z-
dc.date.available2020-09-22T03:00:07Z-
dc.date.issued2020-
dc.identifier.citationTranslational Lung Cancer Research, 2020, v. 9 n. 2, p. 294-305-
dc.identifier.issn2218-6751-
dc.identifier.urihttp://hdl.handle.net/10722/287376-
dc.description.abstractBackground: 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.-
dc.languageeng-
dc.publisherAME Publishing Company. The Journal's web site is located at http://www.tlcr.org/-
dc.relation.ispartofTranslational Lung Cancer Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectHippo-
dc.subjectlarge tumour suppressor (LATS)-
dc.subjectlung cancer-
dc.titleExpression of large tumour suppressor (LATS) kinases modulates chemotherapy response in advanced non-small cell lung cancer-
dc.typeArticle-
dc.identifier.emailKwok, HH: kwokh@hku.hk-
dc.identifier.emailIp, MSM: msmip@hku.hk-
dc.identifier.emailLam, DCL: dcllam@hku.hk-
dc.identifier.authorityIp, MSM=rp00347-
dc.identifier.authorityLam, DCL=rp01345-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.21037/tlcr.2020.03.26-
dc.identifier.pmid32420069-
dc.identifier.pmcidPMC7225163-
dc.identifier.scopuseid_2-s2.0-85086084447-
dc.identifier.hkuros314286-
dc.identifier.volume9-
dc.identifier.issue2-
dc.identifier.spage294-
dc.identifier.epage305-
dc.identifier.isiWOS:000530132900016-
dc.publisher.placeHong Kong-
dc.identifier.issnl2218-6751-

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