{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:11:05Z","timestamp":1791231065156,"version":"4.1.0"},"reference-count":45,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,12,22]]},"abstract":"<jats:p>Invasive carcinomas survive and evade apoptosis despite the absence of an exogenous basement membrane. How epithelial tumors acquire anchorage independence for survival remains poorly defined. Epithelial tumors often secrete abundant amounts of the extracellular matrix protein laminin 5 (LM-5) and frequently express \u03b16\u03b24 integrin. Here, we show that autocrine LM-5 mediates anchorage-independent survival in breast tumors through ligation of a wild-type, but not a cytoplasmic tail\u2013truncated \u03b16\u03b24 integrin. \u03b16\u03b24 integrin does not mediate tumor survival through activation of ERK or AKT. Instead, the cytoplasmic tail of \u03b24 integrin is necessary for basal and epidermal growth factor\u2013induced RAC activity, and RAC mediates tumor survival. Indeed, a constitutively active RAC sustains the viability of mammary tumors lacking functional \u03b21 and \u03b24 integrin through activation of NF\u03baB, and overexpression of NF\u03baB p65 mediates anchorage-independent survival of nonmalignant mammary epithelial cells. Therefore, epithelial tumors could survive in the absence of exogenous basement membrane through autocrine LM-5\u2013\u03b16\u03b24 integrin\u2013RAC\u2013NF\u03baB signaling.<\/jats:p>","DOI":"10.1083\/jcb.200302023","type":"journal-article","created":{"date-parts":[[2003,12,23]],"date-time":"2003-12-23T00:07:21Z","timestamp":1072138041000},"page":"1397-1407","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":171,"title":["Autocrine laminin-5 ligates \u03b16\u03b24 integrin and activates RAC and NF\u03baB to mediate anchorage-independent survival of mammary tumors"],"prefix":"10.1083","volume":"163","author":[{"given":"Nastaran","family":"Zahir","sequence":"first","affiliation":[{"name":"1Department of Pathology and Laboratory Medicine, School of Medicine"},{"name":"2Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnathon N.","family":"Lakins","sequence":"additional","affiliation":[{"name":"1Department of Pathology and Laboratory Medicine, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Russell","sequence":"additional","affiliation":[{"name":"3Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"4Department of Cell Biology, Cytokinetics, Inc., South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WenYu","family":"Ming","sequence":"additional","affiliation":[{"name":"5Wells Center for Pediatrics Research, Indiana University School of Medicine, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrima","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"1Department of Pathology and Laboratory Medicine, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela I.","family":"Rozenberg","sequence":"additional","affiliation":[{"name":"1Department of Pathology and Laboratory Medicine, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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