Mitf regulation of Dia1 controls melanoma proliferation and invasiveness.

By S. Carreira, J. Goodall, L. Denat, M. Rodríguez, P. Nuciforo, K. Hoek, A. Testori, L. Larue, C. Goding. Genes & Development, 2006

596 citations recorded by the source corpus.

It is widely held that cells with metastatic properties such as invasiveness and expression of matrix metalloproteinases arise through the stepwise accumulation of genetic lesions arising from genetic instability and "clonal evolution." By contrast, we show here that in melanomas invasiveness can be regulated epigenetically by the microphthalmia-associated transcription factor, Mitf, via regulation of the DIAPH1 gene encoding the diaphanous-related formin Dia1 that promotes actin polymerization and coordinates the actin cytoskeleton and microtubule networks at the cell periphery. Low Mitf levels lead to down-regulation of Dia1, reorganization of the actin cytoskeleton, and increased ROCK-dependent invasiveness, whereas increased Mitf expression leads to decreased invasiveness. Significantly the regulation of Dia1 by Mitf also controls p27(Kip1)-degradation such that reduced Mitf levels lead to a p27(Kip1)-dependent G1 arrest. Thus Mitf, via regulation of Dia1, can both inhibit invasiveness and promote proliferation. The results imply variations in the repertoire of environmental cues that determine Mitf activity will dictate the differentiation, proliferative, and invasive/migratory potential of melanoma cells through a dynamic epigenetic mechanism.

Subfields: Immunology, Immunology and Allergy, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0eeb4ce3e56a03d95d1e930a953090b32177eefc

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Ossia M. Eichhoff
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Citations in the corpus

In vivo switching of human melanoma cells between proliferative and invasive states. (2008, background): “After knockdown of Mitf expression in a proliferative signature line, the cells gained resistance to TGF-h–mediated inhibition of proliferation (Fig. 3). This correlates with experiments by others who have shown that invasive characteristics are increased in melanoma cells treated with siRNA targeti”
Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF (2013, unknown): “…paradoxically can promote tumorigenesis (e.g., Garraway et al., 2005; Yokoyama et al., 2011), whereas activation of MITF expression in normal melanocytes typically induces differentiation, which likely antagonizes tumorigenesis (D’Orazio et al., 2006; Carreira et al., 2006; Haq and Fisher, 2011).”