Oral communication, CS20 / C92

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Epithelial to mesenchymal - like transition is an earlier cellular response to stress than senescence: potential role as a target for cancer prevention

BACKGROUND AND OBJECTIVES: Epithelial to mesenchymal transition (EMT) is a phenotypic reprogramming thought to enhance cellular invasiveness. In cancer, this process is considered as a late event responsible for the orchestration of metastasis, however its role in tumor initiation is not yet understood. Here we sought to determine whether EMT occurs in premalignant nevi and thus, could be amenable to targeting for the prevention of melanoma. We hypothesized that if EMT plays a role in the formation of premalignant tumors, it must occur before the senescence state that characterizes these lesions. METHODS: In vitro experiments were carried out to study the temporal relationship between these two processes in response to oncogenes and other stressors. Expression of EMT and senescence markers was analyzed in melanoma cell lines and also in nevi specimens. The role of GSK 3 beta as a potential target to inhibit EMT was validated using genetic and pharmacologic approaches. RESULTS: The data indicated that regardless of the stress applied, EMT was induced first, then senescence. Immunohistological analysis indicated that melanocytes within benign nevi expressed mesenchymal markers, suggesting that an EMT-like process may play a role in the biology of these lesions. GSK3 beta was found to facilitate the degradation of Zeb1, a key player in EMT, and inhibit cellular proliferation as well as motility. In addition, activators of GSK3 beta exerted anti-proliferative and anti-EMT activities. CONCLUSION: Findings from this study suggest that: 1. EMT is an earlier cellular response to stress than senescence, 2. an EMT-like process is likely to occur in premalignant tumors, 3. and GSK3 beta may represent a compelling target to disrupt EMT pathways in premalignant and malignant melanoma.

Advertisement from our sponsor: