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Non-angiogenic vascularization enhances blood flow, tumor growth, and metastasis. Although inhibition of focal adhesion kinase (FAK) is a promising anticancer strategy, its effect on non-angiogenic vascularization remains unknown. We aimed to determine if defactinib, an oral selective FAK inhibitor, suppresses tumor growth by inhibiting non-angiogenic vascularization via reduced cell migration in malignant breast cancer cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Non-angiogenic vascularization was evaluated in JIMT-1 and MDA-MB-231 cells. Western blotting, fluorescent immunocytochemistry, cell migration assay, time-lapse microscopy, and tube formation assays were performed to evaluate the effects of defactinib. Cells were transfected with siFAK to evaluate off-target effects. The in vivo effects were assessed in orthotopic mouse tumor models, followed by immunohistochemical staining of excised tumor samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Defactinib induced changes in cell morphology, migration, and the formation of vascular-like structures in JIMT-1 and MDA-MB-231 cells. Phosphorylation of FAK\/PTK2 and its downstream effectors was reduced in defactinib-treated cells. SiRNA-mediated FAK knockdown produced similar effects. Treatment with defactinib suppressed tumor growth in orthotopic mouse tumor models, resulting in tumor shrinkage and reduced macroscopic blood-rich areas. Immunohistochemical staining also revealed a significant reduction in the number of vessels characterized by human serpin family E member 2\u2014a potential indicator of non-angiogenic vascularization\u2014in the defactinib-treated group, with no significant increase in apoptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FAK inhibition was shown to suppress non-angiogenic vascularization. Defactinib has the potential to serve as a novel treatment for malignant breast cancer which is resistant to conventional therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12282-025-01792-6","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T15:51:28Z","timestamp":1761666688000},"page":"188-199","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Targeting focal adhesion kinase inhibits cell migration and non-angiogenic vascularization in malignant breast cancer"],"prefix":"10.1007","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0873-4486","authenticated-orcid":false,"given":"Misato","family":"Masuyama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0832-9877","authenticated-orcid":false,"given":"Masafumi","family":"Shimoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikumi","family":"Seto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Kikumori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanae","family":"Masunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieko","family":"Mishima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Tsukabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuhiro","family":"Yoshinami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Sota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Miyake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Tanei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenzo","family":"Shimazu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"1792_CR1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1177\/1758834010397627","volume":"3","author":"SB Goldfarb","year":"2011","unstructured":"Goldfarb SB, Hudis C, Dickler MN. 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