{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T12:19:21Z","timestamp":1777292361945,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>SATB2 (special AT-rich binding protein 2) functions as a chromatin-associated epigenetic regulator that modulates gene expression, in part by serving as a transcriptional cofactor. This study assessed whether SATB2 overexpression is sufficient to promote in vitro transformation of human mesothelial cells and whether SATB2 suppression in mesothelioma cancer stem cell (CSC)\u2013enriched populations is associated with altered chemoresistance. SATB2 expression was high in human malignant pleural mesothelioma (MPM) cell lines but absent in Met5A mesothelial cells. Ectopic SATB2 expression in Met5A cells was associated with acquisition of malignant and stem cell\u2013like phenotypes, including increased expression of stem cell markers and pluripotency-associated factors, as well as anchorage-independent growth in soft agar and spheroid formation in suspension culture. In contrast, Met5A cells transduced with an empty vector did not form colonies or mesospheres. SATB2 overexpression in Met5A cells was also associated with increased motility, migration, and invasion, accompanied by induction of epithelial\u2013mesenchymal transition (EMT)\u2013related transcription factors relative to empty vector controls. Conversely, shRNA-mediated SATB2 knockdown in an MPM cell line attenuated proliferation, EMT-associated features, and CSC-like characteristics. Chromatin immunoprecipitation assays identified SATB2 occupancy at promoter regions of Bcl2, XIAP, KLF4, c-Myc, NANOG, and SOX2, consistent with a role in transcriptional regulation of genes linked to transformation, pluripotency, cell survival, proliferation, and EMT. In CSC-enriched cells, SATB2 inhibition was associated with increased sensitivity to cisplatin and pemetrexed, concomitant with reduced OCT4 and SOX2 expression. Collectively, these findings support SATB2 as a candidate therapeutic target in MPM and suggest that SATB2 suppression may enhance chemotherapy response when combined with standard agents.<\/jats:p>","DOI":"10.3390\/cells15030283","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:49:44Z","timestamp":1770036584000},"page":"283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SATB2 Induces Malignant Transformation and Cancer Stem Cell Characteristics, and Inhibition of Its Expression Reverses Drug Resistance in Mesothelioma"],"prefix":"10.3390","volume":"15","author":[{"given":"Cynthia","family":"Brown","sequence":"first","affiliation":[{"name":"GLAX LLC, LSU Innovation Park, 8000 Innovation Park Drive, Baton Rouge, LA 70820, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivam","family":"Srivastava","sequence":"additional","affiliation":[{"name":"GLAX LLC, LSU Innovation Park, 8000 Innovation Park Drive, Baton Rouge, LA 70820, USA"},{"name":"Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohit","family":"Srivastava","sequence":"additional","affiliation":[{"name":"GLAX LLC, LSU Innovation Park, 8000 Innovation Park Drive, Baton Rouge, LA 70820, USA"},{"name":"Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76706, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rashmi","family":"Srivastava","sequence":"additional","affiliation":[{"name":"GLAX LLC, LSU Innovation Park, 8000 Innovation Park Drive, Baton Rouge, LA 70820, USA"},{"name":"Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76706, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Morvant","sequence":"additional","affiliation":[{"name":"Department of Surgery, Ochsner Health System, Gretna, LA 70056, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anju","family":"Shrivastava","sequence":"additional","affiliation":[{"name":"St. Joseph\u2019s Hospital and Medical Center, Phoenix, AZ 85013, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakesh K.","family":"Srivastava","sequence":"additional","affiliation":[{"name":"GLAX LLC, LSU Innovation Park, 8000 Innovation Park Drive, Baton Rouge, LA 70820, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s41030-025-00301-6","article-title":"A Diagnostic Approach to Malignant Pleural Mesothelioma","volume":"11","author":"Aujayeb","year":"2025","journal-title":"Pulm. 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