The ‘Yin and Yang’ of Cancer Cell Growth and Mechanosensing
Abstract
Simple Summary
Abstract
1. Introduction
2. The ECM Provides the Biomechanical Context of Tissues and Cells
3. The Mechanical Tumor Microenvironment Affects Tumor Growth
4. ECM Mechanosensing Is a Multi-Step Process
5. Mechanotransduction at Focal Adhesions
5.1. The FAK-Src Complex
5.2. Rho Family GTPases
6. Anchorage-Independence and Mechanosensing Aberrations Characterize Metastatic Cells
7. Which Mechanobiological Processes Underlie Anchorage-Independent Cancer Cell Growth?
8. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Cancer Type | Species | Elevated Kinase Activity | Growth-Associated Signaling Pathways | References (PMID) | |
---|---|---|---|---|---|
FAK | Src | ||||
Lung | Human | + | + | PI3K/Akt | [93,94] |
Human | + | MEK/MAPK | [94,95] | ||
Human | + | YAP/Hippo | [96,97,98,99] | ||
Colorectal | Human | + | + | PI3K/Akt | [100] |
Human | + | EGFR | [101,102] | ||
Human, rat | + | EGFR/ERK | [103] | ||
Human | + | ERK | [104] | ||
Breast | Human | + | STAT3 | [105] | |
Human | + | + | HER receptors/PI3k/Akt /MAPK | [106,107] | |
Human | + | YAP/Hippo | [108,109] | ||
Pancreatic | Human | + | + | Ras/Raf, PI3K/Akt | [81,83,110] |
Human, mouse | + | + | ERK | [108] | |
Human | + | EGFR/Erb2, ERK, STATs, TGF-β | [111,112,113] | ||
Human, mouse | + | EGFR/STAT3 | [114] | ||
Prostate | Human, mouse | + | SFK (Src family kinases) Lyn | [80] | |
Human | + | PI3K/Akt | [115] | ||
Human | + | EGFR/Akt/ERK | [116,117,118] | ||
Mouse | + | MAPK | [119] |
Cancer Type | Adhesion Types | Adhesion Rigidity Dependency | Signaling Pathways | Cancer-Related Effects | In Vitro/In Vivo/Ex Vivo | Publicat-ion |
---|---|---|---|---|---|---|
Lung | FA | N/A | VAV2/FAK/Rac1 | Promotion of metastasis | In vitro: human H1299 and H460 cells In vivo: transplantation in nude mice | [178] |
FA | Promotion of FA formation on soft ECM | FAK | Increase in migration velocity and distance | In vitro: human A549 cells | [179] | |
FA | N/A | Keap1 upregulation of RhoA activity | Inhibition of cell motility caused by FA turnover inhibition | In vitro: human A549 cells | [180] | |
FA | Increase in FA formation and size on stiff ECM | N/A | Decrease in cell motility | In vitro: human H1299 cells | [181] | |
FA & invadopodia | N/A | StarD13/RhoA/ Rac1/FA, SrarD13/Cdc42/ invadopodia | Inhibition of cell motility (immature FA); promotion of cell invasion (invadopodia) | In vitro: human A549 cells | [182] | |
Invadopodia | N/A | Cortactin/ Cdc42/N-WASP | Promotion of cell invasion | In vitro: human H1299 and A549 cells | [183] | |
Breast | FA | Increase in FA formation on stiff ECM | Integrins/PI3K/Akt | Promotion of cell invasion and malignancy | In vitro: human MCF10 and Ha-ras MCF10 AT MEC cells In vivo: MMTV-Neu mice model, transplantation in mice | [29] |
FA | Increase in FA assembly and size on stiff ECM | ERK/Rho/ Src/FAK | Increase in cell growth and perturbation of tissue architecture | In vitro: Human HMT-3522 S1 cells In vivo: Transplantation in transgenic mice | [184] | |
FA | No difference in FA areas across rigidities | N/A | Increase in cell proliferation | In vitro: human MDA-MB-231 cells | [70] | |
Invadopodia | Increase in invadopodia quantity and activity on stiff ECM | Rho/p130Cas/ FAK | Promotion of cellular invasion | In vitro: human MCF10CA1d cells | [185] | |
Invadopodia | Increase in invadopodia formation at ~30 kPa and 1.8 Gpa | N/A | Increase in ECM degradation | In vitro: human MCF10CA1d cells | [186] | |
Invadopodia | Decrease in invadopodia formation in stiff 3D networks | Rac1/ROCK | Increase in cell migration | In vitro: human MDA-MB-231 cells | [187] | |
Pancreatic | FA | No difference in FA areas across rigidities | N/A | Increase in cell proliferation | In vitro: human PANC-1 cells | [70] |
FA | N/A | Inhibition of FA turnover by cAMP | Inhibition of cell migration | In vitro: human PANC-1, BxPC3, Capan-2, MiaPaca-2 and SUIT-2 cells | [188] | |
FA & invadopodia | N/A | Src/FAK/ p130Cas (FA); Src (invadopodia) | Promotion of cellular invasion and ECM degradation by FA | In vitro: human PANC-1 and BxPC3 cells | [189] | |
Invadopodia | N/A | N/A | Presence of invadopodia within human tumors | In vitro: human PANC-1, BxPC3, Capan-2, MiaPaca-2, SU86.86, MRC-5 and L3.6pl cells Ex vivo: human tumor surgical specimen | [190] |
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Amer, M.; Shi, L.; Wolfenson, H. The ‘Yin and Yang’ of Cancer Cell Growth and Mechanosensing. Cancers 2021, 13, 4754. https://doi.org/10.3390/cancers13194754
Amer M, Shi L, Wolfenson H. The ‘Yin and Yang’ of Cancer Cell Growth and Mechanosensing. Cancers. 2021; 13(19):4754. https://doi.org/10.3390/cancers13194754
Chicago/Turabian StyleAmer, Malak, Lidan Shi, and Haguy Wolfenson. 2021. "The ‘Yin and Yang’ of Cancer Cell Growth and Mechanosensing" Cancers 13, no. 19: 4754. https://doi.org/10.3390/cancers13194754
APA StyleAmer, M., Shi, L., & Wolfenson, H. (2021). The ‘Yin and Yang’ of Cancer Cell Growth and Mechanosensing. Cancers, 13(19), 4754. https://doi.org/10.3390/cancers13194754