{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:43:55Z","timestamp":1753868635319,"version":"3.41.2"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","award":["2014044"],"award-info":[{"award-number":["2014044"]}],"id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vemurafenib\u2010induced drug resistance in melanoma has been linked to receptor tyrosine kinase (RTK) upregulation. The MITF and SOX10 genes play roles as master regulators of melanocyte and melanoma development. Here, we aimed to explore the complex mechanisms behind the MITF\/SOX10\u2010controlled RTK\u2010induced drug resistance in melanoma. To achieve this, we used a number of molecular techniques, including melanoma patient data from TCGA, vemurafenib\u2010resistant melanoma cell lines, and knock\u2010down studies. The melanoma cell lines were classified as proliferative or invasive based upon their MITF\/AXL expression activity. We measured the change of expression activity for MITF\/SOX10 and their receptor (AXL\/ERBB3) and ligand (NRG1\/GAS6) targets known to be involved in RTK\u2010induced drug resistance after vemurafenib treatment. We find that melanoma cell lines characterized as proliferative (high MITF low AXL), transform into an invasive (low MITF, high AXL) cell state after vemurafenib resistance, indicating novel feedback loops and advanced compensatory regulation mechanisms between the master regulators, receptors, and ligands involved in vemurafenib\u2010induced resistance. Together, our data disclose fine\u2010tuned mechanisms involved in RTK\u2010facilitated vemurafenib resistance that will be challenging to overcome by using single drug targeting strategies against melanoma.<\/jats:p>","DOI":"10.1002\/cnr2.1736","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T17:30:52Z","timestamp":1666027852000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cooperative induction of receptor tyrosine kinase<scp>s<\/scp> contributes to adaptive <scp>MAPK<\/scp> drug resistance in melanoma through the <scp>PI3K<\/scp> pathway"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3681-4511","authenticated-orcid":false,"given":"Tine Norman","family":"Alver","sequence":"first","affiliation":[{"name":"Department of Tumor Biology, Institute for Cancer Research Oslo University Hospital  Oslo Norway"},{"name":"Department of Cancer Genetics, Institute for Cancer Research Oslo University Hospital  Oslo Norway"},{"name":"Faculty of Medicine University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen\u2010Marie","family":"Heintz","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Institute for Cancer Research Oslo University Hospital  Oslo Norway"},{"name":"Faculty of Medicine University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9103-1077","authenticated-orcid":false,"given":"Eivind","family":"Hovig","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Institute for Cancer Research Oslo University Hospital  Oslo Norway"},{"name":"Department of Informatics University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigurd L.","family":"B\u00f8e","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Oslo University Hospital, The Norwegian Radium Hospital  Oslo 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