{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:45:32Z","timestamp":1785818732653,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa Carlos Chagas Filho"},{"DOI":"10.13039\/501100013904","name":"Swiss Bridge Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013904","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04r8s6n89","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Programa de Oncobiologia\/Funda\u00e7\u00e3o Andr\u00e9 Frauzino de Pesquisas para o C\u00e2ncer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Esophageal squamous cell carcinoma (ESCC) is a highly prevalent malignancy worldwide. Moreover, ESCC remains poorly characterized at the molecular level, which contributes to limited therapeutic options and an overall poor prognosis. In this context, HMGA family members, which are overexpressed in tumors but almost absent in healthy adult tissues, seem to represent promising therapeutic targets. These proteins act by binding to AT-hook DNA-binding motifs and may regulate the expression of several genes associated with tumor progression. Therefore, integrating in silico, translational, and in vitro approaches, we investigated the functional consequences of blocking HMGA2\u2013DNA interaction in ESCC tumor progression by using netropsin, a site-specific ligand for AT-rich DNA regions. Our results demonstrate that netropsin treatment significantly reduced cell viability, migration, and cell cycle progression, thereby promoting apoptosis. Furthermore, netropsin treatment was capable of partially reverting Epithelial\u2013Mesenchymal Transition (EMT) activation associated with HMGA2 expression, by downregulating EMT activators, such as Slug and Twist. Finally, the netropsin treatment sensitizes ESCC cells to chemotherapeutic treatment with 5-Fluorouracil. Taken together, our findings highlight that AT binding-specific blockade could be correlated with the inhibition of HMGA2 and may reveal a promising approach to better understand ESCC progression.<\/jats:p>","DOI":"10.3390\/ijms27156933","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of the AT-Hook DNA-Binding Domain Attenuates HMGA2-Mediated Epithelial Mesenchyme Transition in Esophageal Cancer Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Lucas de Jesus","family":"Lima","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Intera\u00e7\u00f5es Celulares, Instituto de Ci\u00eancias Biom\u00e9dicas, Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Universidade Federal do Rio de Janeiro, Pr\u00e9dio do Centro de Ci\u00eancias da Sa\u00fade\u2014Cidade Universit\u00e1ria, Ilha do Fund\u00e3o, Rua C\u00e9sar Pernetta, 1766 (LS.3.01), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1340-2212","authenticated-orcid":false,"given":"Matheus","family":"Lohan-Code\u00e7o","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Intera\u00e7\u00f5es Celulares, Instituto de Ci\u00eancias Biom\u00e9dicas, Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Universidade Federal do Rio de Janeiro, Pr\u00e9dio do Centro de Ci\u00eancias da Sa\u00fade\u2014Cidade Universit\u00e1ria, Ilha do Fund\u00e3o, Rua C\u00e9sar Pernetta, 1766 (LS.3.01), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-5270","authenticated-orcid":false,"given":"Maria Lu\u00edsa","family":"Barambo 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Rua C\u00e9sar Pernetta, 1766 (LS.3.01), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalia","family":"Meireles Da Costa","sequence":"additional","affiliation":[{"name":"Programa de Carcinog\u00eanese Molecular (PCM), Centro de Pesquisa e Inova\u00e7\u00e3o (CPQI), Instituto Nacional de C\u00e2ncer (INCA), Rua Andr\u00e9 Cavalcanti 37, Centro, Rio de Janeiro 20231-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00eds Felipe","family":"Ribeiro Pinto","sequence":"additional","affiliation":[{"name":"Programa de Carcinog\u00eanese Molecular (PCM), Centro de Pesquisa e Inova\u00e7\u00e3o (CPQI), Instituto Nacional de C\u00e2ncer (INCA), Rua Andr\u00e9 Cavalcanti 37, Centro, Rio de Janeiro 20231-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Eurico","family":"Nasciutti","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Intera\u00e7\u00f5es Celulares, Instituto de Ci\u00eancias Biom\u00e9dicas, Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Universidade Federal do Rio de Janeiro, Pr\u00e9dio do Centro de Ci\u00eancias da Sa\u00fade\u2014Cidade Universit\u00e1ria, Ilha do Fund\u00e3o, Rua C\u00e9sar Pernetta, 1766 (LS.3.01), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Severo","family":"Ramundo","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednica M\u00e9dica, Disciplina de Imunologia Cl\u00ednica e Alergia, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"},{"name":"Laborat\u00f3rio de Imunologia, LIM-19, Instituto do Cora\u00e7\u00e3o (INCOR), Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-900, 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