{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:34:22Z","timestamp":1785429262885,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u00d6sterreichische Krebshilfe Salzburg (Austria)"},{"DOI":"10.13039\/501100011852","name":"SEED-Novel Innovative Ideas and Preparatory Projects Program at Paracelsus Medizinische Privatuniversit\u00e4t","doi-asserted-by":"publisher","award":["2023-SEED-039-Mani"],"award-info":[{"award-number":["2023-SEED-039-Mani"]}],"id":[{"id":"10.13039\/501100011852","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sturge-Weber Foundation (USA)"},{"id":[{"id":"https:\/\/ror.org\/0048mxk03","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Dysregulated G protein-coupled receptor (GPCR) signaling is increasingly implicated as an important driver for oncogenesis. Uveal melanoma (UM) represents a highly metastatic intraocular malignancy primarily driven by activating mutations in G protein family members G\u03b1q\/11. Although Tebentafusp, the first FDA-approved bi-specific T-cell engager for UM, improves survival, its activity is restricted to specific human leukocyte antigen (HLA) alleles, highlighting the need to identify broadly expressed targetable proteins for immunotherapeutic strategies. Here we aimed to define surfaceome and phospho-signaling signatures associated with oncogenic G\u03b1q-signaling. Methods: Heterologous and UM in vitro systems were used to interrogate G\u03b1q-driven changes. HEK293T cells were transfected with wild-type G\u03b1q or the oncogenic G\u03b1q (R183Q) mutant, with surface marker profiles quantified by flow cytometry. Complementary immunophenotyping was performed in the G\u03b1q-mutant UM cell line MP46 and G\u03b111-mutant line MP41. Kinase phosphorylation was assessed in control and G\u03b1q mutant conditions followed by effect size estimation (Hedges\u2019 g), Welch\u2019s t-test, principal component analysis, and Spearman correlation-based network analysis of surface and phosphoprotein readouts. Results: Hyperactive G\u03b1q in HEK293T cells induced graded remodeling of surface protein profiles, including reduced CD56 (NCAM) and CD49c (ITGA3) expression. Similarly, in UM models, MP46 versus MP41 had limited expression of CD56 and CD49c. Moreover, phospho kinase profiling and network analysis identified altered surface-phosphoprotein relationships, including a CD56-p70 S6 kinase association. Conclusions: These data provide new insights into G\u03b1q-driven modulators of UM phenotype of relevance for studies of tumor\u2013microenvironment interaction and metastasis.<\/jats:p>","DOI":"10.3390\/cancers18121891","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:25:17Z","timestamp":1781083517000},"page":"1891","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oncogenic G\u03b1q Signaling Remodels the Tumor Surfaceome and Rewires Intracellular Networks in Uveal Melanoma Models"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3108-3534","authenticated-orcid":false,"given":"Rakesh","family":"Mani","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"},{"name":"Center for Anatomy and Cell Biology, Salzburg and Nuremberg, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Enzinger","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"},{"name":"Center for Anatomy and Cell Biology, Salzburg and Nuremberg, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Th\u00f6mmes","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"},{"name":"Center for Anatomy and Cell Biology, Salzburg and Nuremberg, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Devlit\u0161arov","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"},{"name":"Center for Anatomy and Cell Biology, Salzburg and Nuremberg, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander C.","family":"Rokohl","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"},{"name":"Center for Anatomy and Cell Biology, Salzburg and Nuremberg, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"},{"name":"Department of Ophthalmology, Faculty of Medicine, University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Deisl","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"},{"name":"Center for Anatomy and Cell Biology, Salzburg and Nuremberg, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig M.","family":"Heindl","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"},{"name":"Center for Anatomy and Cell Biology, Salzburg and Nuremberg, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"},{"name":"Department of Ophthalmology, Faculty of Medicine, University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Pruszak","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"},{"name":"Center for Anatomy and Cell Biology, Salzburg and Nuremberg, Paracelsus Medical Private University (PMU), 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41572-020-0158-0","article-title":"Uveal melanoma","volume":"6","author":"Jager","year":"2020","journal-title":"Nat. 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