Loss of p38δ mitogen-activated protein kinase expression promotes oesophageal squamous cell carcinoma proliferation, migration and anchorage-independent growth.

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dc.contributor.authorO'Callaghan, Carol
dc.contributor.authorFanning, Liam J.
dc.contributor.authorHouston, Aileen M.
dc.contributor.authorBarry, Orla P.
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2016-06-17T14:51:15Z
dc.date.available2016-06-17T14:51:15Z
dc.date.issued2013-05-29
dc.date.updated2013-05-30T15:05:33Z
dc.description.abstractOesophageal cancer is an aggressive tumour which responds poorly to both chemotherapy and radiation therapy and has a poor prognosis. Thus, a greater understanding of the biology of oesophageal cancer is needed in order to identify novel therapeutic targets. Among these targets p38 MAPK isoforms are becoming increasingly important for a variety of cellular functions. The physiological functions of p38α and -β are now well documented in contrast to -γ and -δ which are comparatively under-studied and ill-defined. A major obstacle to deciphering the role(s) of the latter two p38 isoforms is the lack of specific chemical activators and inhibitors. In this study, we analysed p38 MAPK isoform expression in oesophageal cancer cell lines as well as human normal and tumour tissue. We observed specifically differential p38δ expression. The role(s) of p38δ and active (phosphorylated) p38δ (p-p38δ) in oesophageal squamous cell carcinoma (OESCC) was delineated using wild-type p38δ as well as active p-p38δ, generated by fusing p38δ to its upstream activator MKK6b(E) via a decapeptide (Gly-Glu)5 linker. OESCC cell lines which are p38δ-negative (KE-3 and -8) grew more quickly than cell lines (KE-6 and -10) which express endogenous p38δ. Re-introduction of p38δ resulted in a time-dependent decrease in OESCC cell proliferation which was exacerbated with p-p38δ. In addition, we observed that p38δ and p-p38δ negatively regulated OESCC cell migration in vitro. Finally both p38δ and p-p38δ altered OESCC anchorage-independent growth. Our results suggest that p38δ and p-p38δ have a role in the suppression of OESCC. Our research may provide a new potential target for the treatment of oesophageal cancer.en
dc.description.sponsorshipHealth Research Board (grant HRA/2009/17).en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO'Callaghan C., Fanning L., Houston A and Barry OPB. (2013) 'Loss of p38 delta mitogen-activated protein kinase expression promotes oesophageal squamous cell carcinoma proliferation, migration and anchorage-independent growth', International Journal of Oncology, 43, pp. 405-415. http://dx.doi.org/10.3892/ijo.2013.1968en
dc.identifier.doi10.3892/ijo.2013.1968
dc.identifier.endpage415en
dc.identifier.issn1019-6439
dc.identifier.issn1791-2423
dc.identifier.journaltitleInternational Journal of Oncologyen
dc.identifier.startpage405en
dc.identifier.urihttps://hdl.handle.net/10468/2757
dc.identifier.volume43en
dc.language.isoenen
dc.publisherSpandidos Publicationsen
dc.rights© O'Callaghan et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].en
dc.rights.urihttps://creativecommons.org/licenses/by-nc/3.0/en
dc.subjectOesophageal canceren
dc.subjectp38 MAPK isoformsen
dc.subjectOesophageal squamous cell carcinomaen
dc.subjectCell migrationen
dc.subjectCell proliferationen
dc.subjectRNAen
dc.subjectp38δ mitogen-activated protein kinaseen
dc.subjectAnchorage-independent growthen
dc.titleLoss of p38δ mitogen-activated protein kinase expression promotes oesophageal squamous cell carcinoma proliferation, migration and anchorage-independent growth.en
dc.typeArticle (peer-reviewed)en
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