MITF – past, present and future
Article first published online: 13 OCT 2010
© 2010 John Wiley & Sons A/S
Pigment Cell & Melanoma Research
Volume 23, Issue 6, page 723, December 2010
How to Cite
Ronai, Z. (2010), MITF – past, present and future. Pigment Cell & Melanoma Research, 23: 723. doi: 10.1111/j.1755-148X.2010.00780.x
- Issue published online: 13 OCT 2010
- Article first published online: 13 OCT 2010
It has been almost a year since Colin Goding completed his tenure as PCMR Editor-in-Chief. Colin took PCMR to the ‘next level,’ where it now competes with PLoS ONE, JID, JBC and the AACR journal family for excellent papers. Colin set a high bar for current and future PCMR Editors, so it is only fitting that we would want to thank him for his hard work over his 5 years as Editor-in-Chief. In recognition of his significant contribution to our understanding of MITF, the PCMR Editorial team has decided to devote this issue to Colin and features four perspectives focused on different aspects of MITF research. Unaware of our plan, Colin agreed to contribute one of them.
Other contributors include Heinz Arnheiter, who provides an MITF history lesson with a surprising review of discoveries related to MITF, most made by serendipity (including its designation as Microphthalmia-associated transcription factor). Erikur Steingrimsson reviews the molecular genetic and phenotypic properties of the mouse MitfMi-Wh mutation, which was generated as part of studies performed during the Manhattan Project. David Fisher updates us on MITF regulation and function following UV-irradiation, a timely topic given the apparent complexity of mechanisms governing MITF function. Lastly, Colin Goding contributes a forward-looking evaluation of MITF’s potential role in melanoma stem cell biology. While developing his earlier rheostat model for MITF (see cover, which was selected and designed by Colin), in collaboration with Keith Hoek, he extends that model to a new concept – namely phenotype switching, in which temporal changes in gene expression serve to explain melanoma plasticity.
Despite the wealth of information now available regarding MITF, there remains much to be discovered. Future studies should address the structure of MITF and its partner proteins, mechanisms regulating its spatial and temporal expression, and likely, additional signaling pathways that control MITF activity. Relevant to the latter, in this issue, Takemori and colleagues reveal a role for the CREB regulators in control of MITF expression and melanogenesis.
This issue also reports advances in melanoma research and therapy. Meenhard Herlyn’s group reveals the selective effect of the B-Raf inhibitor PLX4032, a leading drug in melanoma treatment, on 3D cultures of melanoma harboring the B-Raf 600E mutation. Meenhard’s studies are part of a series of reports addressing properties of this new class of inhibitors, which are summarized in a commentary by Neal Rosen.
While epidemiological studies have suggested that sunscreen use reduces melanoma risk, Glenn Merlino and colleagues provide experimental evidence to support that view by describing the effect of sunscreens on the incidence of UV-induced melanoma development in mice. Graeme Walker addresses the effect of UV-irradiation on melanocytes and demonstrates that their migration from the follicular outer root sheath into the epidermis following UV is impaired in the absence of functional ARF or p53. Consequently, tumors develop without going through the benign stage, as no nevi are formed. A study from the group of Neil Box complements these findings, demonstrating that increased p53 expression, as is seen in Mdm4+/− mice, prevents progression of nevi to malignant and metastatic melanoma. New insight into melanoma progression is provided by Dean Rosenthal’s group, who report that Smad7-positive melanoma cells show decreased β-catenin degradation, resulting in increased N-cadherin expression and inhibition of melanoma invasion.
This issue’s Profile features Boris Bastian, who made important contributions to our understanding of melanoma genetics and their clinical and physiological relevance, as outlined by Meenhard Herlyn. A timely update of the genetic and morphologic features used to classify melanoma is also provided in this issue by Boris Bastian and collaborators.
Finally, we pay a sad tribute to our colleague Estela Medrano, who died in a tragic car accident last month. Estela was a close friend who provided highly valuable advice and served our community by example. Estela mentored many newcomers to the melanoma field and was highly respected by all of her colleagues. I thank Zalfa Abdel Malek and Menashe Bar Eli, who wrote the obituary honoring her achievements.
MITF past, present and future – all are reflected in this issue of PCMR. Our tribute to Colin Goding reflects his innovative contributions to this field as thinker and experimentalist, and as an Editor-in-Chief who brought the melanoma and pigment disciplines together under one roof at PCMR, where collaboration between these fields continues to thrive. Thank you, Colin.