Upwards and onwards

Abstract

The success of a journal is ultimately tied to its appeal to its readership and potential authors. Over the past few years, by publishing News and Views on high profile papers in the field, inserting ‘Melanoma’ into the title and being adopted as the official journal of the Society for Melanoma Research, and generally acting as a focus and forum for debate on key issues, Pigment Cell & Melanoma Research has increased its readership and is now attracting papers from groups that until recently would have submitted elsewhere. The increased awareness of the journal means that papers published in pcr are more widely read and research into pigment cell biology is gaining a higher profile. The most visible manifestation of a journal’s success is the impact factor, used by publishers to trumpet the success of a journal, and by authors as a key determinant of where to submit. With that in mind, it is again satisfying that the impact factor of this journal has risen yet again, to 4.634. The strong upward trend in impact factor reflects increased citation of papers published in pcr and suggests that the journal is achieving its ambition of serving the research community by publishing papers and reviews of increasing significance to the field. The fact that many of the most cited papers and reviews are in the melanoma field also suggests that the decision to court a melanoma audience has benefited the journal as a whole and is making a substantial contribution to its success. One of the most obvious manifestations of genetic diversity is the range of human pigmentation phenotypes as illustrated by this month’s striking cover. It is widely believed that early hominids originated as a hair covered species in Africa, lacking epidermal pigmentation except in exposed sites and that pigmentation evolved to protect skin against photodamage as hair cover diminished. The migration of humans out of Africa subsequently led to a gradual decrease in levels of constitutive pigmentation as a result of the evolutionary pressures arising from the need to synthesise vitamin D. However, the fact that pigmented melanocytes are present in a wide range of sites that are not sun exposed suggests that melanin-loaded pigment cells may have a range of functions not directly related to UV-irradiation. The hypothesis from Elias et al. explores the possibility that stress to the epidermis also contributed substantially to the origins of human pigmentation. Since its isolation in 1994, the gene encoding the microphthalmia-associated transcription factor Mitf has assumed centre stage as a key factor controlling melanocyte development and differentiation. Over recent years, it has also been implicated as a major regulator of cell cycle progression and metastatic potential. Given its importance and its regulation by the MAPkinase and Wnt/β-catenin signaling pathways implicated in both developmental control of the melanocyte lineage and melanoma progression, it seemed inevitable that genetic lesions affecting the MITF gene would be found in melanoma. That prophecy was fulfilled with the observation that amplification of the MITF gene occurs in many melanoma patients, though interestingly even a 100-fold amplification only led to around 1.5-fold increase in MITF protein levels. Nevertheless, the amplification of the MITF gene spurred the quest to find more subtle genetic alterations that would affect MITF activity and consequently melanoma behavior. Now, in this issue, Cronin et al. report that MITF is mutated at several residues in melanoma that lead to altered MITF function. The paper, featured in a News and Views by David Fisher, also highlights mutations in Sox10, a key regulator of MITF expression. Together, the evidence suggests that de-regulation of MITF function or expression is a major determinant of melanoma progression and lends support to the idea that understanding more of the controls operating on MITF may open novel therapeutic avenues.