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Although multiple genomic mutations and epigenetic alterations have been identified, an efficacious molecularly targeted therapy has yet to be established. Therefore, a novel approach is anticipated. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein that is highly expressed in various cancers. In this study, we evaluated bladder cancer patient samples and found that GPNMB protein abundance is associated with high\u2010grade tumors, and both univariate and multivariate analyses showed that GPNMB is a prognostic factor. Furthermore, the prognosis of patients with high GPNMB levels was significantly poorer in those with nonmuscle invasive bladder cancer (NMIBC) than in those with muscle invasive bladder cancer (MIBC). We then demonstrated that knockdown of GPNMB in MIBC cell lines with high GPNMB inhibits cellular migration and invasion, whereas overexpression of GPNMB further enhances cellular migration and invasion in MIBC cell lines with originally low GPNMB. Therefore, we propose that GPNMB is one of multiple driver molecules in the acquisition of cellular migratory and invasive potential in bladder cancers. Moreover, we revealed that the tyrosine residue in the hemi\u2010immunoreceptor tyrosine\u2010based activation motif (hemITAM) is required for GPNMB\u2010induced cellular motility.<\/jats:p>","DOI":"10.1111\/pin.13419","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T10:15:39Z","timestamp":1710843339000},"page":"262-273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Glycoprotein nonmetastatic melanoma protein B impacts the malignant potential of bladder cancer cells through its hem\u2010immunoreceptor tyrosine\u2010based activation motif"],"prefix":"10.1111","volume":"74","author":[{"given":"Tomokazu","family":"Kimura","sequence":"first","affiliation":[{"name":"Department of Urology University of Tsukuba Ibaraki Japan"},{"name":"Department of Experimental Pathology, Institute of Medicine University of Tsukuba Ibaraki 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