{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:36:05Z","timestamp":1785404165785,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000915","name":"Richard King Mellon Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100000915","id-type":"DOI","asserted-by":"publisher"}]},{"award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/03qevzg44","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Thea Post Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Morton E. Goulder Research Endowment Fund","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), also known as protein tyrosine phosphatase non-receptor type 6, functions as a tumor suppressor in breast, hepatocellular, and prostate cancers and an oncogene in glioblastoma and cervical cancer. A previous analysis of The Cancer Genome Atlas (TCGA) dataset revealed that lower SHP-1 transcript levels in bladder tumors were associated with poorer overall survival. Methods: This study aimed to evaluate the role of SHP-1 in bladder cancer and to assess the functional impact of its forced expression and knockdown in bladder carcinoma cell lines. SHP-1 expression was assessed in 19 bladder cancer cell lines and 26 bladder tissues. Lentiviral transduction was used to knock down or overexpress SHP-1 in four cell lines, followed by Western blot analysis of SHP-1 and pAkt\/Akt protein expression. Results: SHP-1 protein levels were significantly lower in highly invasive cell lines (p &lt; 0.001) and muscle-invasive tumors (p &lt; 0.05). Functional studies demonstrated that SHP-1 modulation influenced the epithelial\u2013mesenchymal transition (EMT) phenotype. SHP-1 expression was positively correlated with E-cadherin expression (p &lt; 0.001) and negatively correlated with N-cadherin (p &lt; 0.01) and Vimentin (p &lt; 0.05) expression. Alteration of SHP-1 expression in bladder cancer cell lines affected proliferation, invasion, and migration (p &lt; 0.05). RNA-seq analysis of the transduced cell lines revealed enrichment of gene sets related to EMT and signaling pathways involving MYC, PI3K, Akt, and mTOR. Furthermore, SHP-1 alteration impacted pAkt\/Akt ratios (p &lt; 0.05). Conclusions: Collectively, lower SHP-1 protein expression correlated with more aggressive phenotypes in bladder cancer cell lines and bladder tumors. In our limited dataset, reduced SHP-1 expression correlated with muscle-invasive disease, suggesting a potential link to more advanced tumor biology, consistent with TCGA associating reduced SHP-1 transcript expression to poorer survival rates. Our data provide preliminary functional evidence that SHP-1 may modulate Akt signaling in bladder cancer. Together, these results support further investigation of SHP-1 as a possible tumor suppressor, candidate prognostic biomarker, and potential therapeutic target in bladder cancer.<\/jats:p>","DOI":"10.3390\/cancers18091401","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:26:41Z","timestamp":1777382801000},"page":"1401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evidence for a Tumor-Suppressive Role of SHP-1 in EMT Regulation in Bladder Cancer Cells"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4356-7924","authenticated-orcid":false,"given":"Kailey","family":"Hooper","sequence":"first","affiliation":[{"name":"Department of Translational Research, Lahey Hospital & Medical Center, Burlington, MA 01805, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"McNall","sequence":"additional","affiliation":[{"name":"Department of Urology, Lahey Hospital & Medical Center, Burlington, MA 01805, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1552-1197","authenticated-orcid":false,"given":"Daniel","family":"Pohl","sequence":"additional","affiliation":[{"name":"Department of Urology, Lahey Hospital & Medical Center, Burlington, MA 01805, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Lahey Hospital & Medical Center, Burlington, MA 01805, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3122-2875","authenticated-orcid":false,"given":"Eric","family":"Burks","sequence":"additional","affiliation":[{"name":"Department of Pathology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Rieger-Christ","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Lahey Hospital & Medical Center, Burlington, MA 01805, USA"},{"name":"Department of Urology, Lahey Hospital & Medical Center, Burlington, MA 01805, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref_1","first-page":"e70043","article-title":"Cancer Statistics, 2026","volume":"76","author":"Siegel","year":"2026","journal-title":"CA Cancer J. 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