Integration of mechanical and ECM microenvironment signals in the determination of cancer stem cell states
Open accessAbstract
Purpose of review Cancer stem cells (CSCs) are increasingly understood to play a central role in tumor progression. Growing evidence implicates tumor microenvironments as a source of signals that regulate or even impose CSC states on tumor cells. This review explores points of integration for microenvironment-derived signals that are thought to regulate CSCs in carcinomas.Recent findings CSC states are directly regulated by the mechanical properties and extra cellular matrix (ECM) composition of tumor microenvironments that promote CSC growth and survival, which may explain some modes of therapeutic resistance. CSCs sense mechanical forces and ECM composition through integrins and other cell surface receptors, which then activate a number of intracellular signaling pathways. The relevant signaling events are dynamic and context-dependent.Summary CSCs are thought to drive cancer metastases and therapeutic resistance. Cells that are in CSC states and more differentiated states appear to be reversible and conditional upon the components of the tumor microenvironment. Signals imposed by tumor microenvironment are of a combinatorial nature, ultimately representing the integration of multiple physical and chemical signals. Comprehensive understanding of the tumor microenvironment-imposed signaling that maintains cells in CSC states may guide future therapeutic interventions.
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The matrix supports spheroid assembly and imposes physical constraints that activate intracellular signaling cascades, including MAPK, PI3K/Akt, and YAP/TAZ pathways.
“The matrix not only supports spheroid assembly but also imposes physical constraints that activate intracellular signaling cascades, including MAPK, PI3K/Akt, and YAP/TAZ pathways [214,215,216].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [214]
The “Signaling pathways > FAK” and “Hippo pathway and YAP/TAZ” sections (page numbers unavailable) describe ECM and mechanical cues affecting MAPK/ERK, PI3K/Akt, and YAP/TAZ signaling. The paper also says YAP and TAZ promote tumor spheroid growth, but it does not say that the matrix supports spheroid assembly or that physical constraints imposed during assembly activate those pathways. (LLM, conf=0.86)
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“The matrix not only supports spheroid assembly but also imposes physical constraints that activate intracellular signaling cascades, including MAPK, PI3K/Akt, and YAP/TAZ pathways [214–216].”
- Authors
- Jokela, T. A., & LaBarge, M. A.
- Affiliations
- City Of Hope National Medical Center (US)
- Corresponding author
- LaBarge, Mark A.
- Venue
- Current Stem Cell Reports
- Published
- 2020-11-23
- Volume
- 7
- Issue
- 1
- Pages
- 39-47
- ISSN
- 2198-7866 (ISSN-L)
- PMC
- PMC7993397
- OpenAlex
- W3106905377
- Cited by
- 24
- References
- 92
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 1 · 2023: 6 · 2022: 4 · 2021: 1
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Stem Cell Reports (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Human Genome Research Institute (U54HG008100)
- National Cancer Institute (U01CA244109)
- National Institute of Biomedical Imaging and Bioengineering (R01EB024989)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- cancer stem cells, tumor microenvironment, extracellular matrix, mechanotransduction, integrins, cell surface receptors, intracellular signaling, treatment resistance, metastasis, carcinoma
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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