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Loss of these contacts induces anoikis, a specific form of apoptosis. Tumor cells acquire resistance to anoikis, enabling them to survive without anchorage, invade the vascular system, and colonize distant organs in a process known as metastasis. Activation of the PI3K\/Akt signaling pathway is the most common mechanism underlying the acquisition of anoikis resistance in cancer cells. The role of phosphoinositide 3-kinase (PI3K) in cancer is highlighted by the frequent mutation of the gene encoding the p110\u03b1 catalytic subunit in the most common human cancers. In this study, we aimed to elucidate the role of PI3K (p110\u03b1 catalytic subunit) in the acquisition of the anoikis-resistant phenotype and in the regulation of cellular characteristics directly related to tumorigenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      To this end, we performed\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      gene silencing in anoikis-resistant endothelial cells. Consequently, these cells exhibited a reversal of malignancy-associated traits, including morphological characteristics, anoikis resistance, clonogenic potential, proliferation rate, invasiveness, and adhesive capacity, resembling those of wild-type endothelial cells. Furthermore, we observed an increased rate of apoptosis, accompanied by changes in the expression of pro- and anti-apoptotic molecules, as well as increased caspase activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In summary, our findings demonstrate that\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      silencing reverses key features of the anoikis-resistant endothelial cell phenotype and provides new insights into the molecular mechanisms underlying anoikis resistance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                    <jats:p>\n                      Comparative diagram of the main characteristics of anoikis-resistant endothelial cells before and after\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      silencing. Some elements of the graphical abstract were adapted from Servier Medical Art (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/smart.servier.com\/\" ext-link-type=\"uri\">https:\/\/smart.servier.com\/<\/jats:ext-link>\n                      <jats:underline>,<\/jats:underline>\n                      accessed 26 August 2025).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11033-026-12680-3","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T11:16:44Z","timestamp":1788002204000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PIK3CA silencing restores anoikis sensitivity in endothelial cells"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1554-3684","authenticated-orcid":false,"given":"Diego Mauro Carneiro","family":"Pereira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-0804","authenticated-orcid":false,"given":"Ana Paula","family":"de Sousa Mesquita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3906-6528","authenticated-orcid":false,"given":"Amanda","family":"da Silva Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9023-2483","authenticated-orcid":false,"given":"Luc\u00e9lia","family":"Donatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7569-2166","authenticated-orcid":false,"given":"Helena Bonciani","family":"Nader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0840-5702","authenticated-orcid":false,"given":"Carla Cristina","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"12680_CR1","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1083\/jcb.124.4.619","volume":"124","author":"S Frisch","year":"1994","unstructured":"Frisch S, Francis H (1994) Disruption of epithelial cell-matrix interactions induces apoptosis. 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