ArticleProceedings of the National Academy of Sciences of the United States of America2009
Tunable interplay between epidermal growth factor and cell-cell contact governs the spatial dynamics of epithelial growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 80 citations in OpenAlex.
- Pre-Loading of Cells via Vapor Sublimation and the Deposition Polymerization Process with a 3D Porous Scaffold for Cell Cultures.ACS biomaterials science & engineering · 2025Article
- Same same but different? How blood and lymphatic vessels induce cell contact inhibition.Biochemical Society transactions · 2025Review
- On the control of cell proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- An agent-based modelling framework to study growth mechanisms inRoyal Society open science · 2024Article
- The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation.International journal of molecular sciences · 2024Review
- Collective heterogeneity of mitochondrial potential in contact inhibition of proliferation.Biophysical journal · 2023Article
- Sustained postconfluent culture of human mammary epithelial cells enriches for luminal and c-Kit+ subtypes.Breast cancer research : BCR · 2023Article
- Cadherins and catenins in cancer: connecting cancer pathways and tumor microenvironment.Frontiers in cell and developmental biology · 2023Review
- The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and Function.Frontiers in cell and developmental biology · 2022Review
- Control of tissue homeostasis, tumorigenesis, and degeneration by coupled bidirectional bistable switches.PLoS computational biology · 2021Article
- The Hippo pathway regulates density-dependent proliferation of iPSC-derived cardiac myocytes.Scientific reports · 2021Article
- Molecular control of cell density-mediated exit to quiescence.Cell reports · 2021Article
- Epithelial tissue geometry directs emergence of bioelectric field and pattern of proliferation.Molecular biology of the cell · 2020Article
- Cracking the Cell Death Code.Cold Spring Harbor perspectives in biology · 2020Review
- Review
- Dynamics of transcriptome changes during subcutaneous preadipocyte differentiation in ducks.BMC genomics · 2019Article
- Context-explorer: Analysis of spatially organized protein expression in high-throughput screens.PLoS computational biology · 2019Article
- Spatial Proliferation of Epithelial Cells Is Regulated by E-Cadherin Force.Biophysical journal · 2018Article
- E-cadherin in contact inhibition and cancer.Oncogene · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Contact-inhibition of proliferation constrains epithelial tissue growth, and the loss of contact-inhibition is a hallmark of cancer cells. In most physiological scenarios, cell-cell contact inhibits proliferation in the presence of other growth-promoting cues, such as soluble growth factors (GFs). How cells quantitatively reconcile the opposing effects of cell-cell contact and GFs, such as epidermal growth factor (EGF), remains unclear. Here, using quantitative analysis of single cells within multicellular clusters, we show that contact is not a "master switch" that overrides EGF. Only when EGF recedes below a threshold level, contact inhibits proliferation, causing spatial patterns in cell cycle activity within epithelial cell clusters. Furthermore, we demonstrate that the onset of contact-inhibition and the timing of spatial patterns in proliferation may be reengineered. Using micropatterned surfaces to amplify cell-cell interactions, we induce contact-inhibition at a higher threshold level of EGF. Using a complementary molecular genetics approach to enhance cell-cell interactions by overexpressing E-cadherin also increases the threshold level of EGF at which contact-inhibition is triggered. These results lead us to propose a state diagram in which epithelial cells transition from a contact-uninhibited state to a contact-inhibited state at a critical threshold level of EGF, a property that may be tuned by modulating the extent of cell-cell contacts. This quantitative model of contact-inhibition has direct implications for how tissue size may be determined and deregulated during development and tumor formation, respectively, and provides design principles for engineering epithelial tissue growth in applications such as tissue engineering.
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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.