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Based on previous results, which showed expression by human ovarian granulosa cells,\n                      <jats:italic>w<\/jats:italic>\n                      e studied human TRPV2 in human granulosa cell tumors (GCTs) and derived cells (KGN cells). GCTs are rare ovarian tumors, for which neither specific therapies, nor adequate markers are available.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed primary GCTs, including a panel of 63 GCT samples, and KGN cells. We performed immunohisto-\/cytochemistry, RT-PCR, Western blotting and measurements of intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      levels. We studied consequences of CRISPR\/Cas9-based deletion of TRPV2 on cell proliferation, migration and macropinocytotic behavior, examined changes in steroid hormone production, and determined corresponding alterations of the proteome of these cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that GCTs express TRPV2 to a large percentage (95%). To examine roles of TRPV2, we turned to the human GCT-derived KGN cell line. CRISPR\/Cas9-based deletion of TRPV2 resulted in larger cell size, increases in proliferation, migration and macropinocytotic behavior, changes in steroid production, and corresponding alterations of the proteome of these cells. Deletion of TRPV2 also significantly reduced susceptibility to cell death, which was induced within hours by cannabidiol (CBD), a preferred ligand of TRPV2, in a concentration- and time-dependent manner. However, cell death was not completely abolished and the analysis of the TRPV2-interactome suggested the voltage-dependent anion channel 1 (VDAC1) as a further target for CBD. VDAC1, as part of a cascade involving formation and persistent opening of the mitochondrial permeability transition pore (mPTP), is linked to cell death. A blocker of mPTP formation, cyclosporin A, significantly decreased the vulnerability of KGN cells to CBD-induced cell death. TRPV2-depleted KGN cells treated with cyclosporin A became almost completely insensitive to the effects of CBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results reveal a role of TRPV2 in GCT cells. Thus, CBD causes cell death in KGN cells via direct TRPV2 activation and via interaction with VDAC1. Expression of TRPV2 may thus be a novel marker to distinguish subtypes of GCTs. Furthermore, TRPV2 represents a novel drug target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-026-02729-y","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T05:24:55Z","timestamp":1770873895000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["TRPV2 regulates cell fate in the human granulosa-like tumor cell line KGN: implications for granulosa cell tumors and cannabidiol"],"prefix":"10.1186","volume":"24","author":[{"given":"Katja","family":"Eubler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sree Priyanka","family":"Jeevanandan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina Magdalena","family":"Caban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Bernd","family":"St\u00f6ckl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte Benjamin","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Kreitmair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Scholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Mayr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Renkawitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Welter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"M\u00fcller-Taubenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Fr\u00f6hlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9388-4639","authenticated-orcid":false,"given":"Artur","family":"Mayerhofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"2729_CR1","doi-asserted-by":"publisher","first-page":"jcs258372","DOI":"10.1242\/jcs.258372","volume":"134","author":"L Yue","year":"2021","unstructured":"Yue L, Xu H. 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These samples were described in a previous report [\n                      \n                      ], all patients agreed to the scientific use of the tissue and the study was approved by the ethical committee of LMU (project 390-15). In addition, archival material of tissue microarrays (TMAs) consisting of 63 GCT samples was used for immunohistochemistry. This part of the study was approved by the ethical committee of LMU (projects 20-697 & 20-895). The use of human primary granulosa cells (hGCs) was approved by the ethical committee of LMU (project 20\u2013697) and patients had agreed to the use of the cells. All experiments were performed in accordance with relevant guidelines and regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"139"}}