Mechanotransduction in cancer

Chin, LiKang; Xia, Yuntao; Discher, Dennis E.; Janmey, Paul A.

doi:10.1016/j.coche.2016.01.011

Cited by 145 publications

(117 citation statements)

References 63 publications

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“…In 2D culture models of soft or stiff matrix, cytoskeleton forces and linkages convey mechanical information from outside-to-inside: both lung cancer and primary mesenchymal stem cells exhibit higher lamin-A,C levels when grown on stiff matrix. Similar results have been found for some human cancer cell lines in vitro and in xenografts in vivo 16, 20, 79 . Three-dimensional xenografts of a human glioblastoma line in stiff mouse subcutaneous tissue lead to significantly higher levels of lamin-A,C than xenografts in mouse brain which is soft 16, 79 .…”

Section: Introductionsupporting

confidence: 88%

Nuclear Lamins in Cancer

et al. 2016

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Dysmorphic nuclei are commonly seen in cancers and provide strong motivation for studying the main structural proteins of nuclei, the lamins, in cancer. Past studies have also demonstrated the significance of microenvironment mechanics to cancer progression, which is extremely interesting because the lamina was recently shown to be mechanosensitive. Here, we review current knowledge relating cancer progression to lamina biophysics. Lamin levels can constrain cancer cell migration in 3D and thereby impede tumor growth, and lamins can also protect a cancer cell's genome. In addition, lamins can influence transcriptional regulators (RAR, SRF, YAP/TAZ) and chromosome conformation in lamina associated domains. Further investigation of the roles for lamins in cancer and even DNA damage may lead to new therapies or at least to a clearer understanding of lamins as bio-markers in cancer progression.

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Section: Introductionsupporting

confidence: 88%

Nuclear Lamins in Cancer

et al. 2016

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“…Glioma cell activation by substrate stiffness has previously been reported 19,41 and is similar to that reported in studies of numerous other cell types. 46 Consistent with these results, a correlation between glioblastoma aggressiveness and the stiffness of ECM enriched in tenascin C has been reported. 47 Other studies suggest that the relevance of an in vitro mechanical response to the in vivo setting in the brain is obscured by the fact that the elastic modulus of normal brain is very low, on the order of a few hundred Pascal, and the stiffness of human glioma tissue is highly variable, with different studies concluding either stiffening or softening of the tumor when measured by elastography in vivo 13–18 and no greater than that of normal brain when measured ex vivo from biopsy sections.…”

Section: Discussionsupporting

confidence: 65%

Soft Substrates Containing Hyaluronan Mimic the Effects of Increased Stiffness on Morphology, Motility, and Proliferation of Glioma Cells

et al. 2017

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Unlike many other cancer cells that grow in tumors characterized by an abnormally stiff collagen-enriched stroma, glioma cells proliferate and migrate in the much softer environment of the brain, which generally lacks the filamentous protein matrix characteristic of breast, liver, colorectal, and other types of cancer. Glial cell-derived tumors and the cells derived from them are highly heterogeneous and variable in their mechanical properties, their response to treatments, and their properties in vitro. Some glioma samples are stiffer than normal brain when measured ex vivo, but even those that are soft in vitro stiffen after deformation by pressure gradients that arise in the tumor environment in vivo. Such mechanical differences can strongly alter the phenotype of cultured glioma cells. Alternatively, chemical signaling might elicit the same phenotype as increased stiffness by activating intracellular messengers common to both initial stimuli. In this study the responses of three different human glioma cell lines to changes in substrate stiffness are compared with their responses on very soft substrates composed of a combination of hyaluronic acid and a specific integrin ligand, either laminin or collagen I. By quantifying cell morphology, stiffness, motility, proliferation, and secretion of the cytokine IL-8, glioma cell responses to increased stiffness are shown to be nearly identically elicited by substrates containing hyaluronic acid, even in the absence of increased stiffness. PI3-kinase activity was required for the response to hyaluronan but not to stiffness. This outcome suggests that hyaluronic acid can trigger the same cellular response, as can be obtained by mechanical force transduced from a stiff environment, and demonstrates that chemical and mechanical features of the tumor microenvironment can achieve equivalent reactions in cancer cells.

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“…[28] However, most studies employing the blood flow environment have focused on endothelial cells, [29][30][31] and the biological changes of CTCs under hydrodynamic environment are understudied. While FSS can selectively kill less resistant cells, FSS on cells can also lead to biological changes.…”

Section: Discussionmentioning

confidence: 99%

Fluid Shear Stress Induces Drug Resistance to Doxorubicin and Paclitaxel in the Breast Cancer Cell Line MCF7

Triantafillu

Park

Kim

2018

Advanced Therapeutics

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Circulating tumor cells (CTCs) are known to have cancer stem cell (CSC) properties and survive physiological conditions of fluid shear stress (FSS). However, current chemotherapy screening techniques do not adequately recapitulate this FSS environment and are not predictive of a drug response. In this study, MCF7 and MDA-MB-231 cells under FSS are used as an in vitro model of CTCs. The effects of doxorubicin (DOX) and paclitaxel on sheared cells using WST8 assay and stemness (CD44 + /CD24 − ) and apoptosis (Annexin V + /7-AAD + ) using flow cytometry are tested. Quantitative polymerase chain reaction is used to test gene expression. It is shown that suspension-cultured and FSS treated MCF7 cells increase in drug resistance, especially with DOX. There is a synergistic increase in the CD44 + /CD24 − CSC-like population and an increase in drug resistance-related gene expression in MCF7 cells co-treated with FSS and drugs. There is also a correlated increase in STAT3 and NANOG expression under FSS. To the best of the authors' knowledge, this is the first report to suggest that the increase in CSC-like cells from FSS contributes to drug resistance via the STAT3/NANOG pathway.This increase in CTC drug resistance also highlights the importance of implementing FSS, which is unavailable in current drug screening techniques.

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Mechanotransduction in cancer

Cited by 145 publications

References 63 publications

Nuclear Lamins in Cancer

Nuclear Lamins in Cancer

Soft Substrates Containing Hyaluronan Mimic the Effects of Increased Stiffness on Morphology, Motility, and Proliferation of Glioma Cells

Fluid Shear Stress Induces Drug Resistance to Doxorubicin and Paclitaxel in the Breast Cancer Cell Line MCF7

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