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Yet, therapies for metastatic melanoma are still insufficient so that new concepts are essential. Malignant transformation of melanocytes and melanoma progression are intimately linked to the cutaneous <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> landscape and its dysregulation in tumour lesions. The <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> landscape of normal skin is characterized by a large <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> gradient of up to 3 <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> units between surface and dermis. The Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchanger <jats:styled-content style=\"fixed-case\">NHE<\/jats:styled-content>1 is one of the major contributors of acidity in superficial skin layers. It is also activated by the most frequent mutation in melanoma, <jats:styled-content style=\"fixed-case\">BRAF<jats:sup>V<\/jats:sup><\/jats:styled-content><jats:sup>600E<\/jats:sup>, thereby causing <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> dysregulation during melanoma initiation. Melanoma progression is supported by an extracellular acidification and\/or <jats:styled-content style=\"fixed-case\">NHE<\/jats:styled-content>1 activity which promote the escape of single melanoma cells from the primary tumour, migration and metastatic spreading. We propose that viewing melanoma against the background of the acid\u2010base physiology of the skin provides a better understanding of the pathophysiology of this disease and allows the development of novel therapeutic concepts.<\/jats:p>","DOI":"10.1111\/apha.13105","type":"journal-article","created":{"date-parts":[[2018,5,26]],"date-time":"2018-05-26T14:15:31Z","timestamp":1527344131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Cutaneous <scp>pH<\/scp> landscape as a facilitator of melanoma initiation and progression"],"prefix":"10.1111","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1578-914X","authenticated-orcid":false,"given":"A.","family":"Koch","sequence":"first","affiliation":[{"name":"Institute of Physiology II University of M\u00fcnster M\u00fcnster 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