Mechanisms of melanoma initiation and dissemination

By : Julien ABLAIN

Date : Thursday 20 April 2023

1:30 PM - 2:30 PM

Place : Amphi Gustave Roussy

My laboratory aims to discover new vulnerabilities of cancer cells by better understanding the mechanisms of tumor initiation and progression. Next-generation sequencing of large numbers of human tumors has defined the landscape of genomic alterations in many cancers. Yet there is a need to functionally characterize driver lesions in order to develop new therapies. This issue is particularly significant in melanoma, the tumor type that exhibits the most genetic alterations and that remains associated with poor prognosis, especially at advanced stages. The zebrafish is uniquely positioned to systematically probe the complex genetics of melanoma in vivo. We have contributed to devising new tools that enable to rapidly model any genotype found in human melanomas in adult zebrafish. This modeling has allowed us to establish the negative MAPK pathway regulator SPRED1 as a new melanoma tumor-suppressor gene, whose deletion confers resistance to current targeted therapies. Recently, we have identified the adherens junction gene NECTIN1 as an important metastasis-suppressor, whose loss cooperates with the local depletion of the growth factor IGF1 to promote melanoma dissemination. These results uncover a mechanism by which melanoma cells integrate signals from the tumor microenvironment with their own adhesion capacity to decide whether to stay or spread. Further deciphering of the different cues that regulate the behaviors of cancer cells may both inform the biology of tumor development and open new therapeutic perspectives, as metastasis remains the leading cause of mortality for patients with cancer.

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