{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:06:30Z","timestamp":1780477590573,"version":"3.54.1"},"reference-count":31,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Oklahoma State University College of Veterinary Medicine, Department of Physiological Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>HIV-1 Tat-interactive protein of 60 kDa (TIP60) is a lysine acetyltransferase protein that can acetylate histone and non-histone proteins. This study highlights TIP60\u2019s role in regulating colorectal cancer (CRC) stemness. The depletion of TIP60 resulted in a marked decrease in cellular proliferation, highlighting TIP60\u2019s involvement in the progression of CRC. Additionally, the loss of TIP60 impacted colony formation, transitioning from densely packed structures to dispersed spindle networks along with the loss of E-cadherin, indicating its role in the epithelial\u2013mesenchymal transition (EMT). Three-dimensional culture models suggest that TIP60 is vital for spheroid formation, highlighting its importance in maintaining cancer stem cell properties in CRC. TIP60-depleted cells showed increased invasion in a 3D basement membrane extract (BME) invasion matrix, demonstrating its essential role in cellular invasiveness. Mechanistically, the reduction of TIP60 resulted in a decrease in CD44 expression, a critical marker for cancer stem cells (CSCs). Notably, CD44 overexpression restored the efficiency of spheroid formation and cell proliferation while reversing the EMT phenotype. Developing the TIP60-CD44 axis as a therapeutic target to treat CRC stemness and metastasis will help decrease the burden due to the deadly disease.<\/jats:p>","DOI":"10.3390\/cells14100686","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T09:56:19Z","timestamp":1746784579000},"page":"686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The TIP60-CD44 Axis Modulates Colorectal Cancer Stemness"],"prefix":"10.3390","volume":"14","author":[{"given":"Asad","family":"Mohammad","sequence":"first","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5093-4843","authenticated-orcid":false,"given":"Sudhakar","family":"Jha","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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