O'Callaghan, C,Fanning, LJ,Houston, A,Barry, OP

2013

August

International Journal of Oncology

Loss of p38 delta mitogen-activated protein kinase expression promotes oesophageal squamous cell carcinoma proliferation, migration and anchorage-independent growth

Validated

()

oesophageal cancer p38 delta mitogen-activated protein kinase proliferation migration anchorage-independent growth MAP KINASE C-JUN P38 CANCER P38-ALPHA PATHWAY ISOFORMS DIFFERENTIATION TRANSCRIPTION INVOLVEMENT

43

405

415

Oesophageal 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 p38 alpha and -beta are now well documented in contrast to -gamma and -delta 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 p38 delta expression. The role(s) of p38 delta and active (phosphorylated) p38 delta (p-p38 delta) in oesophageal squamous cell carcinoma (OESCC) was delineated using wildtype p38 delta as well as active p-p38 delta, generated by fusing p38 delta to its upstream activator MKK6b(E) via a decapeptide (Gly-Glu)(5) linker. OESCC cell lines which are p38 delta-negative (KE-3 and -8) grew more quickly than cell lines (KE-6 and -10) which express endogenous p38 delta. Re-introduction of p38 delta resulted in a time-dependent decrease in OESCC cell proliferation which was exacerbated with p-p38 delta. In addition, we observed that p38 delta and p-p38 delta negatively regulated OESCC cell migration in vitro. Finally both p38 delta and p-p38 delta altered OESCC anchorage-independent growth. Our results suggest that p38 delta and p-p38 delta have a role in the suppression of OESCC. Our research may provide a new potential target for the treatment of oesophageal cancer.

10.3892/ijo.2013.1968