Matrix stiffness mediates stemness characteristics via activating the Yes‐associated protein in colorectal cancer cells

Tan, Fengbo; Huang, Yan; Pei, Qian; Liu, Heli; Pei, Haiping; Zhu, Hong

doi:10.1002/jcb.27532

Cited by 43 publications

(45 citation statements)

References 30 publications

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“…Most of the main mechanosensitive phenotypes induced through YAP/TAZ lean on integrin-mediated adhesion [11]. YAP and TAZ can also be directly regulated by the extracellular matrix (ECM) stiffness and YAP itself is involved in FA assembly [15,20,21] (Figure 1).…”

Section: Mechanotransduction: Overview and Structural Basismentioning

confidence: 99%

Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease

Cobbaut

Karagil

Bruno

et al. 2020

Cells

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In order to ascertain their external environment, cells and tissues have the capability to sense and process a variety of stresses, including stretching and compression forces. These mechanical forces, as experienced by cells and tissues, are then converted into biochemical signals within the cell, leading to a number of cellular mechanisms being activated, including proliferation, differentiation and migration. If the conversion of mechanical cues into biochemical signals is perturbed in any way, then this can be potentially implicated in chronic disease development and processes such as neurological disorders, cancer and obesity. This review will focus on how the interplay between mechanotransduction, cellular structure, metabolism and signalling cascades led by the Hippo-YAP/TAZ axis can lead to a number of chronic diseases and suggest how we can target various pathways in order to design therapeutic targets for these debilitating diseases and conditions.

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Section: Mechanotransduction: Overview and Structural Basismentioning

confidence: 99%

Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease

Cobbaut

Karagil

Bruno

et al. 2020

Cells

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“…31 In order to explore the effects of matrix stiffness on cancer stem cells and whether YAP activity was involved, we have recently conducted a series of experiments. 32 In our experiment, we found that ECM stiffness remarkably upregulates the expression of CSC markers. Further experiment showed that matrix stiffness can increase the amount of dephosphorylated YAP and its entry into the nucleus.…”

Section: Effect Of Matrix Stiffness On the Characteristics Of Cancer mentioning

confidence: 49%

<p>Matrix Stiffness and Colorectal Cancer</p>

Liu¹,

Pei²,

Tan³

2020

OTT

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In recent years, a growing consensus is emerging that the mechanical microenvironment of tumors is far more critical in the onset of tumor, tumor progression, invasion, and metastasis. Matrix stiffness, one of the sources of mechanical stimulation, affects tumor cells as well as non-tumor cells in multiple different molecular signaling pathways in solid tumors such as colorectal tumors, which lead to tumor invasion and metastasis, immune evasion and drug resistance. This review will illustrate the relationship between matrix stiffness and colorectal cancer from the following aspects. First, briefly introduce the mechanical microenvironment and colorectal cancer, then explain the origin of colorectal cancer extracellular matrix stiffness, and then synthesize the study of matrix stiffness of colorectal cancer in recent years to elaborate the effects of extracellular matrix stiffness in colorectal cancer's biological behavior and signaling pathways, and finally we will discuss the transformation treatment for the matrix stiffness of colorectal cancer. An in-depth understanding of matrix stiffness and colorectal cancer can help researchers conduct further experiments to find new targets for the treatment of colorectal cancer.

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“…In line with these observations, some studies have correlated the different expression of extracellular matrix proteins and its stiffness to aberrant activation of the TGF-β pathway, accompanied by an expression of determined integrins, with enhancing cancer cell stemness and invasion [67][68][69]. In addition, tumor-initiating cells are more resistant to detachment-induced anoikis and exhibit phenotypic plasticity to move between epithelial to mesenchymal states [69,70].…”

Section: Discussionmentioning

confidence: 85%

“…In addition, tumor-initiating cells are more resistant to detachment-induced anoikis and exhibit phenotypic plasticity to move between epithelial to mesenchymal states [69,70]. Tumor-initiating cells are the driver for drug resistance, cancer relapses, and metastasis, which remains to occur in some cases of breast cancer [69][70][71]. Taken together, this evidence suggests a tight association among the EMT phenotype induced by MDA-MB-231-derived extracellular matrix, through αvβ3 integrin activity and tumor-initiating cells, but further investigation is required in future studies.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Matrix Derived from High Metastatic Human Breast Cancer Triggers Epithelial-Mesenchymal Transition in Epithelial Breast Cancer Cells through αvβ3 Integrin

Brandão-Costa

Helal-Neto

Vieira

et al. 2020

IJMS

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Alterations in the composition and architecture of the extracellular matrix (ECM) can influence cancer growth and dissemination. During epithelial-mesenchymal transition (EMT), epithelial cells assume a mesenchymal cell phenotype, changing their adhesion profiles from cell-cell contacts to cell-matrix interactions, contributing to metastasis. Breast cancer cells present at different stages of differentiation, producing distinct ECMs in the same tumor mass. However, the contribution of ECM derived from metastatic tumor cells to EMT is unclear. Here, we showed the mechanisms involved in the interaction of MCF-7, a low-metastatic, epithelial breast cancer cell line, with the ECM produced by a high metastatic breast tumor cell, MDA-MB-231 (MDA-ECM). MDA-ECM induced morphological changes in MCF-7 cells, decreased the levels of E-cadherin, up-regulated mesenchymal markers, and augmented cell migration. These changes were accompanied by the activation of integrin-associated signaling, with increased phosphorylation of FAK, ERK, and AKT and activation canonical TGF-β receptor signaling, enhancing phosphorylation of SMAD2 and SMAD4 nuclear translocation in MCF-7 cells. Treatment with Kistrin (Kr), a specific ligand of integrin αvβ3 EMT induced by MDA-ECM, inhibited TGF-β receptor signaling in treated MCF-7 cells. Our results revealed that after interaction with the ECM produced by a high metastatic breast cancer cell, MCF-7 cells lost their characteristic epithelial phenotype undergoing EMT, an effect modulated by integrin signaling in crosstalk with TGF-β receptor signaling pathway. The data evidenced novel potential targets for antimetastatic breast cancer therapies.During metastasis, tumor epithelial cells must acquire a migratory profile assuming a mesenchymal phenotype. The epithelial to mesenchymal transition (EMT) encompasses a well-coordinated series of molecular changes that lead epithelial cells to lose E-cadherin expression, acquire increased vimentin, fibronectin, and N-cadherin expression, and rearrange cortical actin structures, increasing their migratory capacity, characteristics of mesenchymal cells [5,6]. Considered the main inductor of EMT in tumor cells, TGF-β-through the activation of their receptors-regulates two different pathways. The non-canonical pathway is related to the activation of focal adhesion kinase (FAK), ERK/MAPK, and AKT signaling. While the canonical pathway is initiated by the phosphorylation of the cytoplasmic signaling molecules, SMAD2 is followed by recruitment and activation of R-SMAD (SMAD3 associated with SMAD2). This complex is phosphorylated and then associates with SMAD4 through the MH2 domain, triggering its translocation to the nucleus. These two signaling pathways regulate the transcription of different genes that culminate in the characteristic morphological and functional changes of EMT [7,8].The crosstalk between TGF-β receptors and other receptors, such as integrin, can modulate EMT in different cell types [9]. Integrins are transmembrane adhesive receptors that are ab...

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Matrix stiffness mediates stemness characteristics via activating the Yes‐associated protein in colorectal cancer cells

Cited by 43 publications

References 30 publications

Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease

Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease

<p>Matrix Stiffness and Colorectal Cancer</p>

Extracellular Matrix Derived from High Metastatic Human Breast Cancer Triggers Epithelial-Mesenchymal Transition in Epithelial Breast Cancer Cells through αvβ3 Integrin

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