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Leptin also plays a key role in tumor vascularization by promoting vasculogenic mimicry (VM). During tumor progression, leptin activates several signaling pathways, including the focal adhesion kinase (FAK) pathway. This study aimed to determine whether leptin promotes and regulates angiogenesis and VM through the FAK pathway. We used the chick chorioallantoic membrane (CAM) as a model to evaluate blood vessel formation and to induce tumors to assess angiogenic expression. Matrigel-based cell cultures were used to analyze the formation of tubular structures characteristic of VM. The expression of specific markers was then evaluated for each process. These models were employed with or without the inhibitor PF-573,228. Our results showed that leptin enhances the sprouting, branching, and vasodilation of blood vessels via FAK signaling by increasing the expression of vascular endothelial growth factor (VEGF) and N-cadherin in tumors derived from MCF-7 and MDA-MB-231 cells. Furthermore, leptin stimulation promoted tubular-type VM in MCF-7 cells and matrix-type VM in MDA-MB-231 cells; the former was dependent on FAK signaling. Lastly, leptin increased the levels of several proteins associated with angiogenesis and VM, including TIE-1, MMP-9, VE-cadherin, ANG-2, VEGF, and VEGFR1. In conclusion, leptin promotes tumor vascularization in breast cancer through angiogenesis and VM, in a manner dependent on FAK signaling<\/jats:p>","DOI":"10.1007\/s12032-026-03370-y","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:08:34Z","timestamp":1787987314000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FAK regulates leptin-induced angiogenesis and vasculogenic mimicry in breast cancer"],"prefix":"10.1007","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5677-8958","authenticated-orcid":false,"given":"Ana K.","family":"Herrera-Vargas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0403-537X","authenticated-orcid":false,"given":"Ricardo","family":"Jaime-Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Rodr\u00edguez-Leviz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6247-8590","authenticated-orcid":false,"given":"Miguel A.","family":"Mendoza-Catal\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1813-9062","authenticated-orcid":false,"given":"Monserrat","family":"Olea-Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8314-8996","authenticated-orcid":false,"given":"Laura","family":"Villavicencio-Guzm\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-8148","authenticated-orcid":false,"given":"Marcela","family":"Salazar-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1995-0308","authenticated-orcid":false,"given":"Carlos C.","family":"Pati\u00f1o-Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4911-0545","authenticated-orcid":false,"given":"Napole\u00f3n","family":"Navarro-Tito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"3370_CR1","doi-asserted-by":"publisher","first-page":"341","DOI":"10.17605\/OSF.IO\/PW6ME","volume":"4","author":"AK Kurbonov","year":"2023","unstructured":"Kurbonov AK, Olimjonova GO, Khusainova KJ, Khamzaeva NT. 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