ArticleProceedings of the National Academy of Sciences of the United States of America1998
Reciprocal interactions between beta1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 309 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
309 citing papers in PubMed, 1 synthesis or guideline pooled it, 640 citations in OpenAlex.
- Pooled it
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- 3D bioprinting for cancer modeling and drug screening.Biomarker research · 2026Review
- Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026Review
- 3D bioprinting of cell-laden constructs: technologies, bioink design, and biomedical applications.Biomedical materials (Bristol, England) · 2025Review
- Impact of different 3D culture environments on spheroid morphology, drug response, and invasion in pancreatic cancer cells.BMC research notes · 2025Article
- Invasin-functionalized PIC hydrogels enable long-term 3D culture of epithelial organoids.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Engineered basement membrane mimetic hydrogels to study mammary epithelial morphogenesis and invasion.Science advances · 2025Article
- An Agrin-YAP/TAZ Rigidity Sensing Module Drives EGFR-Addicted Lung Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Review
- Integrin-activatingProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The isobaric tags for relative and absolute quantification-based quantitative proteomics of fresh tissue-derived secretome in hepatocellular carcinoma.Archives of medical science : AMS · 2025Article
- TGF-β effects on adipogenesis of 3T3-L1 cells differ in 2D and 3D cell culture conditions.FEBS open bio · 2024Article
- Review
- Review
- Assessing Drug Uptake and Response Differences in 2D and 3D Cellular Environments Using Stimulated Raman Scattering Microscopy.Analytical chemistry · 2024Article
- The epithelial polarity axis controls the resting membrane potential and Cl- co-transport in breast glandular structures.Journal of cell science · 2024Article
- Irradiated Mammary Spheroids Elucidate Mechanisms of Macrophage-Mediated Breast Cancer Recurrence.Cellular and molecular bioengineering · 2023Article
249 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
Abstract
Anchorage and growth factor independence are cardinal features of the transformed phenotype. Although it is logical that the two pathways must be coregulated in normal tissues to maintain homeostasis, this has not been demonstrated directly. We showed previously that down-modulation of beta1-integrin signaling reverted the malignant behavior of a human breast tumor cell line (T4-2) derived from phenotypically normal cells (HMT-3522) and led to growth arrest in a three-dimensional (3D) basement membrane assay in which the cells formed tissue-like acini (14). Here, we show that there is a bidirectional cross-modulation of beta1-integrin and epidermal growth factor receptor (EGFR) signaling via the mitogen-activated protein kinase (MAPK) pathway. The reciprocal modulation does not occur in monolayer (2D) cultures. Antibody-mediated inhibition of either of these receptors in the tumor cells, or inhibition of MAPK kinase, induced a concomitant down-regulation of both receptors, followed by growth-arrest and restoration of normal breast tissue morphogenesis. Cross-modulation and tissue morphogenesis were associated with attenuation of EGF-induced transient MAPK activation. To specifically test EGFR and beta1-integrin interdependency, EGFR was overexpressed in nonmalignant cells, leading to disruption of morphogenesis and a compensatory up-regulation of beta1-integrin expression, again only in 3D. Our results indicate that when breast cells are spatially organized as a result of contact with basement membrane, the signaling pathways become coupled and bidirectional. They further explain why breast cells fail to differentiate in monolayer cultures in which these events are mostly uncoupled. Moreover, in a subset of tumor cells in which these pathways are misregulated but functional, the cells could be "normalized" by manipulating either pathway.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.