Cited by 24Cancer Cells and MetastasisCellular Mechanics and InteractionsMesenchymal stem cell research

Integration of mechanical and ECM microenvironment signals in the determination of cancer stem cell states

Open access
Jokela, Tiina A., LaBarge, Mark A.·2021·Current Stem Cell Reports

Abstract

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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Integrity signals

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Crossref · 10.1007/s40778-020-00182-2

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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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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)
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
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

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