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We show that <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>rai1 and <jats:styled-content style=\"fixed-case\">STIM<\/jats:styled-content>2 are highly expressed and control store\u2010operated <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup> entry in human melanoma. Lower extracellular <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup> or silencing of <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>rai1\/<jats:styled-content style=\"fixed-case\">STIM<\/jats:styled-content>2 caused a decrease in intracellular <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>, which correlated with enhanced proliferation and increased expression of microphthalmia\u2010associated transcription factor, a marker for proliferative melanoma phenotype. In contrast, the invasive and migratory potential of melanoma cells was reduced upon silencing of <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>rai1 and\/or <jats:styled-content style=\"fixed-case\">STIM<\/jats:styled-content>2. Accordingly, markers for a non\u2010proliferative, tumor\u2010maintaining phenotype such as <jats:styled-content style=\"fixed-case\">JARID<\/jats:styled-content>1<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>rn2 decreased. Immunohistochemical staining of primary melanomas and lymph node metastases revealed a heterogeneous distribution of <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>rai1 and <jats:styled-content style=\"fixed-case\">STIM<\/jats:styled-content>2 with elevated expression in the invasive rim of the tumor. In summary, our results support a dynamic model in which <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>rai1 and <jats:styled-content style=\"fixed-case\">STIM<\/jats:styled-content>2 inversely control melanoma growth and invasion. Pharmacological tuning of <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>rai1 and particularly <jats:styled-content style=\"fixed-case\">STIM<\/jats:styled-content>2 might thus prevent metastatic spread and render melanomas more susceptible to conventional therapy.<\/jats:p>","DOI":"10.1111\/pcmr.12222","type":"journal-article","created":{"date-parts":[[2014,1,29]],"date-time":"2014-01-29T08:06:40Z","timestamp":1390982800000},"page":"442-453","source":"Crossref","is-referenced-by-count":92,"title":["Inverse regulation of melanoma growth and migration by <scp>O<\/scp>rai1\/<scp>STIM<\/scp>2\u2010dependent calcium entry"],"prefix":"10.1111","volume":"27","author":[{"given":"Hedwig","family":"Stanisz","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology University Hospital of the Saarland Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Saul","sequence":"additional","affiliation":[{"name":"Department of Biophysics School of Medicine Saarland University Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia S. 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