{"entity":{"id":"paper-weaver-j-cell-biol","kind":"paper","name":"Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies","aka":[],"tldr":"Paper cited by two term pages, indexed on Europe PMC as PubMed record 9105051 and published in The Journal of cell biology; the citing pages link this DOI, which is how the record was matched.","summary":"In a recently developed human breast cancer model, treatment of tumor cells in a 3-dimensional culture with inhibitory beta1-integrin antibody or its Fab fragments led to a striking morphological and functional reversion to a normal phenotype. A stimulatory beta1-integrin antibody proved to be ineffective. The newly formed reverted acini re-assembled a basement membrane and re-established E-cadherin-catenin complexes, and re-organized their cytoskeletons. At the same time they downregulated cyclin D1, upregulated p21(cip,wat-1), and stopped growing. Tumor cells treated with the same antibody and injected into nude mice had significantly reduced number and size of tumors in nude mice. The tissue distribution of other integrins was also normalized, suggesting the existence of intimate interactions between the different integrin pathways as well as adherens junctions. On the other hand, nonmalignant cells when treated with either alpha6 or beta4 function altering antibodies continued to grow, and had disorganized colony morphologies resembling the untreated tumor colonies. This shows a significant role of the alpha6/beta4 heterodimer in directing polarity and tissue structure. The observed phenotypes were reversible when the cells were disassociated and the antibodies removed. Our results illustrate that the extracellular matrix and its receptors dictate the phenotype of mammary epithelial cells, and thus in this model system the tissue phenotype is dominant over the cellular genotype.\n\nIndexed on Europe PMC as PubMed record 9105051 (DOI 10.1083/jcb.137.1.231). Matched by DOI alone: two term pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Cell Biol 1997","url":"https://doi.org/10.1083/jcb.137.1.231"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9105051/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/9105051"}],"tags":["europepmc-ingest"],"related":["mechanical-theory-of-cancer","tissue-organisation-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Journal of cell biology","year":1997,"doi":"10.1083/jcb.137.1.231","pmid":"9105051","authors":"Weaver VM, Petersen OW, Wang F, et al.","paperType":"basic","findings":[],"whatItMeans":"Two term pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-weaver-j-cell-biol/","neighbours":{"term":[{"id":"mechanical-theory-of-cancer","kind":"term","name":"Mechanical theory: stiffness, pressure and force as causes","route":"/terms/mechanical-theory-of-cancer/"},{"id":"tissue-organisation-field-theory","kind":"term","name":"Tissue organisation field theory (Sonnenschein and Soto)","route":"/terms/tissue-organisation-field-theory/"}]}}