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Analysis of The Cancer Genome Atlas (TCGA) data revealed a significant positive correlation between PANX1 mRNA and core Hippo components, Yes\u2010associated protein 1 [YAP], Transcriptional coactivator with PDZ\u2010binding motif [TAZ], and Hippo scaffold, Ras GTPase\u2010activating\u2010like protein IQGAP1 [IQGAP1], in invasive cutaneous melanoma and breast carcinoma. Furthermore, we demonstrated that PANX1 expression is upregulated in invasive melanoma cell lines and is associated with increased YAP protein levels. Notably, our investigations uncovered a previously unrecognized interaction between endogenous PANX1 and the Hippo scaffold protein IQGAP1 in melanoma cells. Moreover, our findings revealed that IQGAP1 exhibits differential expression in melanoma cells and plays a regulatory role in cellular morphology. Functional studies involving PANX1 knockdown provided compelling evidence that PANX1 modulates YAP protein levels and its cotranscriptional activity in melanoma and breast carcinoma cells. Importantly, our study highlights the potential therapeutic significance of targeting PANX1. Pharmacological inhibition of PANX1 using selective FDA\u2010approved inhibitors or PANX1 knockdown reduced YAP levels in melanoma cells. Furthermore, our Clariom\u2122 S analysis unveiled key genes implicated in cell proliferation, such as neuroglin1 (NRG1), \u03b2\u2010galactoside binding protein and galectin\u20103 (LGALS3), that are affected in PANX1\u2010deficient cells. In summary, our investigation delves into the intricate interplay between PANX1 and YAP in the context of invasive melanoma, offering valuable insights into potential therapeutic strategies for effective treatment.<\/jats:p>","DOI":"10.1111\/febs.17396","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T11:49:01Z","timestamp":1736423341000},"page":"1633-1653","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pannexin 1 crosstalk with the Hippo pathway in malignant melanoma"],"prefix":"10.1111","volume":"292","author":[{"given":"Samar","family":"Sayedyahossein","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine National Institutes of Health  Bethesda MD USA"},{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry The University of Western Ontario  London 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