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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The kallikrein\u2013kinin system (KKS) and the kallikrein-related peptidase (KLK) family are interconnected proteolytic networks that regulate inflammatory signaling, vascular permeability, extracellular matrix remodeling, and tissue barrier dynamics. Beyond their classical vasoactive and inflammatory functions, accumulating evidence indicates that kinin peptides, including bradykinin, Lys-bradykinin, and their des-Arg9 metabolites, together with selected KLKs, modulate cell\u2013cell and cell\u2013extracellular matrix adhesion. Through B1 and B2 kinin receptor activation, the KKS influences endothelial adhesion molecule expression, leukocyte integrin activation, neutrophil trafficking, focal adhesion kinase\/Src signaling, cytoskeletal remodeling, and matrix metalloproteinase activity. In parallel, KLKs directly reshape the adhesive microenvironment by cleaving junctional proteins, including E-cadherin and desmosomal components, and extracellular matrix substrates such as fibronectin, laminin, vitronectin, fibrinogen, and collagens. These coordinated actions affect epithelial and endothelial barrier integrity, leukocyte transmigration, angiogenesis, fibrosis, epithelial\u2013mesenchymal transition, tumor cell migration, invasion, and metastatic dissemination. This review critically summarizes current evidence linking KKS and KLK activity to adhesion-dependent processes in inflammation and cancer, emphasizing how proteolytic signaling may either preserve tissue homeostasis or promote pathological barrier disruption depending on cellular context, receptor expression, protease activity, and microenvironmental cues. Understanding these mechanisms may refine the identification of adhesion-related biomarkers and support the development of targeted therapeutic strategies for inflammatory disorders, fibrotic remodeling, and cancer progression.<\/jats:p>","DOI":"10.3390\/ijms27167282","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"7282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Kallikrein\u2013Kinin System: Proteolytic Orchestrators of Tissue Barrier Disruption in Inflammation and Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Areli","family":"C\u00e1rdenas-Oyarzo","sequence":"first","affiliation":[{"name":"Centro Integrativo de Biolog\u00eda y Qu\u00edmica Aplicada (CIBQA), Facultad de Ciencias de la Salud, Universidad Bernardo OHiggins, General Gana 1702, Santiago 8370854, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos D.","family":"Figueroa","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Pathology, Institute of Anatomy, Histology & Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia 5090000, Chile"},{"name":"The Kallikrein House, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Huilcam\u00e1n","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Faculty of Health Sciences, Universidad Bernardo O\u2019Higgins, Santiago 8370854, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4646-5682","authenticated-orcid":false,"given":"Larissa","family":"Turones","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Pathology, Institute of Anatomy, Histology & Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia 5090000, Chile"},{"name":"Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6336-5571","authenticated-orcid":false,"given":"Sergio","family":"Mart\u00ednez-Huenchull\u00e1n","sequence":"additional","affiliation":[{"name":"School of Physical Therapy, Universidad San Sebasti\u00e1n, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2519-7570","authenticated-orcid":false,"given":"Pamela","family":"Ehrenfeld","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Pathology, Institute of Anatomy, Histology & Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia 5090000, Chile"},{"name":"Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/JLB.2MR0220-549R","article-title":"ICAM-1: A Master Regulator of Cellular Responses in Inflammation, Injury Resolution, and Tumorigenesis","volume":"108","author":"Bui","year":"2020","journal-title":"J. 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