{"entity":{"id":"basement-membrane-tissue-barriers","kind":"pathway","name":"Basement membrane & tissue barriers","aka":[],"tldr":"Every organ keeps its lining cells behind a thin, dense sheet of protein called the basement membrane. A tumour that has not crossed it is 'in situ' and essentially curable; crossing it is the moment cancer becomes invasive.","summary":"Epithelia sit on a basement membrane of laminin, collagen IV, nidogen and perlecan anchored by integrins (α6β4 at hemidesmosomes) and dystroglycan, beneath which lies interstitial stroma. Polarity (apical-basal), E-cadherin junctions, and contact inhibition keep cells in place. Carcinoma in situ (DCIS, CIN3, Barrett's dysplasia) respects the sheet; invasion requires protease-driven breach (MMP2/9/14, uPA) at invadopodia, loss of polarity (PAR3, SCRIB), integrin switching and EMT-like changes, often assisted by CAFs and macrophages that widen the gap. Myoepithelial cells in breast add a second barrier. Staging encodes this (Tis versus T1) and screening programmes aim to find lesions before the breach.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Basement_membrane","links":[{"label":"Kelley et al., Traversing the basement membrane in vivo (J Cell Biol 2014)","url":"https://doi.org/10.1083/jcb.201311112"}],"tags":["mechanism","mechanics-atlas"],"related":[],"cancers":["cervical","esophageal","breast-hr-positive","urothelial"],"sections":[],"technologies":["colposcopy-excision","endoscopic-resection","precancer-ablation","hpv-vaccine","histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["emt","invasion-ecm-degradation","field-cancerisation"],"terms":["tnm-staging","cin-hsil","barretts-esophagus","stage-shift"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-kelley-j-cell-biol"],"journals":[],"dependsOn":[],"notes":[],"analogy":"A shop floor with a locked glass floor beneath it. Staff (epithelial cells) can be unruly upstairs and it is still contained; the emergency begins when someone cuts through the glass into the building services below, where the plumbing (blood and lymph vessels) runs.","nodes":[{"id":"epi","label":"Polarised epithelium","x":15,"y":15},{"id":"junc","label":"E-cadherin junctions","x":45,"y":15},{"id":"bm","label":"Basement membrane","x":45,"y":45},{"id":"int","label":"Integrins / hemidesmosomes","x":15,"y":45},{"id":"cis","label":"Carcinoma in situ","x":78,"y":15},{"id":"mmp","label":"MMPs, uPA, invadopodia","x":78,"y":45},{"id":"stroma","label":"Stroma, vessels","x":78,"y":80},{"id":"inv","label":"Invasive carcinoma","x":45,"y":80},{"id":"myo","label":"Myoepithelial layer","x":15,"y":80}],"edges":[{"from":"epi","to":"junc","type":"activates"},{"from":"int","to":"bm","type":"activates"},{"from":"junc","to":"cis","type":"inhibits"},{"from":"bm","to":"inv","type":"inhibits"},{"from":"myo","to":"inv","type":"inhibits"},{"from":"cis","to":"mmp","type":"activates"},{"from":"mmp","to":"bm","type":"inhibits"},{"from":"mmp","to":"stroma","type":"activates"},{"from":"stroma","to":"inv","type":"activates"},{"from":"cis","to":"inv","type":"activates"}],"interventions":["Screening and excision of in situ disease (colposcopy, DCIS surgery, endoscopic resection) before the breach","HPV vaccination removes the commonest driver of cervical in situ lesions","MMP inhibitors failed clinically in the 1990s; invasion is now approached via FAK, integrin and stromal targets","Staging (Tis vs T1) and margins encode whether the barrier was crossed"]},"route":"/pathways/basement-membrane-tissue-barriers/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"}],"technology":[{"id":"colposcopy-excision","kind":"technology","name":"Colposcopy and excisional treatment (LEEP/LLETZ, cone)","route":"/technologies/colposcopy-excision/"},{"id":"endoscopic-resection","kind":"technology","name":"Endoscopic resection (EMR / ESD)","route":"/technologies/endoscopic-resection/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"hpv-vaccine","kind":"technology","name":"HPV & HBV vaccination","route":"/technologies/hpv-vaccine/"},{"id":"precancer-ablation","kind":"technology","name":"Thermal ablation and cryotherapy for cervical precancer","route":"/technologies/precancer-ablation/"}],"pathway":[{"id":"emt","kind":"pathway","name":"Epithelial-mesenchymal transition & drug efflux","route":"/pathways/emt/"},{"id":"field-cancerisation","kind":"pathway","name":"Field cancerisation","route":"/pathways/field-cancerisation/"},{"id":"invasion-ecm-degradation","kind":"pathway","name":"Invasion: proteases, adhesion & the invasive front","route":"/pathways/invasion-ecm-degradation/"}],"term":[{"id":"barretts-esophagus","kind":"term","name":"Barrett's oesophagus","route":"/terms/barretts-esophagus/"},{"id":"cin-hsil","kind":"term","name":"Cervical precancer (CIN, HSIL/LSIL)","route":"/terms/cin-hsil/"},{"id":"mechanical-theory-of-cancer","kind":"term","name":"Mechanical theory: stiffness, pressure and force as causes","route":"/terms/mechanical-theory-of-cancer/"},{"id":"stage-shift","kind":"term","name":"Stage shift","route":"/terms/stage-shift/"},{"id":"tissue-organisation-field-theory","kind":"term","name":"Tissue organisation field theory (Sonnenschein and Soto)","route":"/terms/tissue-organisation-field-theory/"},{"id":"tnm-staging","kind":"term","name":"TNM staging","route":"/terms/tnm-staging/"}],"paper":[{"id":"paper-kelley-j-cell-biol","kind":"paper","name":"Traversing the basement membrane in vivo: a diversity of strategies","route":"/key-papers/paper-kelley-j-cell-biol/"}]}}