Extracellular matrix stiffness and Wnt/β-catenin signaling in physiology and disease

2020 ◽  
Vol 48 (3) ◽  
pp. 1187-1198
Author(s):  
Pablo Astudillo
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
The Other ◽  
Matrix Stiffness ◽  
Mechanical Stiffness ◽  
Mechanical Signal ◽  
Wnt Ligands ◽  
Extracellular Matrix Stiffness

The Wnt/β-catenin signaling pathway plays fundamental roles during development, stem cell differentiation, and homeostasis, and its abnormal activation can lead to diseases. In recent years, it has become clear that this pathway integrates signals not only from Wnt ligands but also from other proteins and signaling routes. For instance, Wnt/β-catenin signaling involves YAP and TAZ, which are transcription factors with crucial roles in mechanotransduction. On the other hand, Wnt/β-catenin signaling is also modulated by integrins. Therefore, mechanical signals might similarly modulate the Wnt/β-catenin pathway. However, and despite the relevance that mechanosensitive Wnt/β-catenin signaling might have during physiology and diseases such as cancer, the role of mechanical cues on Wnt/β-catenin signaling has received less attention. This review aims to summarize recent evidence regarding the modulation of the Wnt/β-catenin signaling by a specific type of mechanical signal, the stiffness of the extracellular matrix. The review shows that mechanical stiffness can indeed modulate this pathway in several cell types, through differential expression of Wnt ligands, receptors and inhibitors, as well as by modulating β-catenin levels. However, the specific mechanisms are yet to be fully elucidated.

scholarly journals The role of extracellular matrix stiffness in megakaryocyte and platelet development and function

2018 ◽  
Vol 93 (3) ◽  
pp. 430-441 ◽  
Author(s):  
Orly Leiva ◽  
Catherine Leon ◽  
Seng Kah Ng ◽  
Pierre Mangin ◽  
Christian Gachet ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Stiffness ◽  
Extracellular Matrix Stiffness ◽  
And Function

scholarly journals Syndecans and Pancreatic Ductal Adenocarcinoma

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino
Keyword(s):  
Extracellular Matrix ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Types ◽  
Ductal Adenocarcinoma ◽  
Physiological Processes ◽  
Extracellular Matrix Components ◽  
Detection And Diagnosis ◽  
And Migration ◽  
Early Detection And Diagnosis

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.

scholarly journals Precancerous niche (PCN), a product of fibrosis with remodeling by incessant chronic inflammation

4open ◽  
2019 ◽  
Vol 2 ◽  
pp. 11 ◽  
Author(s):  
Björn L.D.M. Brücher ◽  
Ijaz S. Jamall
Keyword(s):  
Extracellular Matrix ◽  
Chronic Inflammation ◽  
Genetic Material ◽  
Cell Communication ◽  
Cell Types ◽  
Complex Signaling ◽  
Different Cell Types ◽  
Multiple Signaling ◽  
Extracellular Environment

Fibroblasts are actively involved in the creation of the stroma and the extracellular matrix which are important for cell adhesion, cell–cell communication, and tissue metabolism. The role of fibrosis in carcinogenesis can be examined by analogy to tissues of various cancers. The orchestration of letters in the interplay of manifold components with signaling and crosstalk is incompletely understood but available evidence suggests a hitherto underappreciated role for fibrosis in carcinogenesis. Complex signaling and crosstalk by pathogenic stimuli evoke persistent subclinical inflammation, which in turn, results in a cascade of different cell types, ubiquitous proteins and their corresponding enzymes, cytokine releases, and multiple signaling pathways promoting the onset of fibrosis. There is considerable evidence that the body's attempt to resolve such a modified extracellular environment leads to further disruption of homeostasis and the genesis of the precancerous niche as part of the six-step process that describes carcinogenesis. The precancerous niche is formed and can be understood to develop as a result of (1) pathogenic stimulus, (2) chronic inflammation, and (3) fibrosis with alterations of the extracellular matrix, stromal rigidity, and mechano-transduction. This is why carcinogenesis is not just a process of aberrant cell growth with damaged genetic material but the role of the PCN in its entirety reveals how carcinogenesis can occur without invoking the need for somatic mutations.

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