Response to Mechanical Cues by Interplay of YAP/TAZ Transcription Factors and Key Mechanical Checkpoints of the Cell:A Comprehensive Review

Many factors including growth factors (GF), scaffold materials, and chemical and physical cues determine the cell behaviors. For many years, growth factors have been considered as the pivotal cell behavior regulators, whereas recent studies emphasize also the key role of physical factors such as mechanical forces, cell shape, surface topographies, and extracellular matrix (ECM) in regulating the cell proliferation, apoptosis, differentiation, etc. through mechanotransduction pathways. In this process, the cell morphology and mechanical properties of the cell's micro/ nano-environments and ECM can be conveyed to the nucleus by regulating transcriptional factors such as Yes-associated protein and transcriptional coactivator with PDZ-binding motif (TAZ). Generally, YAP/TAZ activity is considered as the key factor for the growth of whole organs, however, recent studies have also repeatedly addressed the role of YAP/TAZ in mechanotransduction. In this review, the biological functions of the YAP/TAZ pathway and its contribution to the mechanotransduction and cell behavior regulation in response to the mechanical cues have been summarized. Also, the role of key mechanical checkpoints in the cell including focal adhesions, cytoskeletal tension, Rho small GTPases, and nuclear membrane protein elements involved in the transfer of environmental mechanical cues from the cell surface to the nucleus and their effect in regulating the YAP/TAZ activity are discussed.

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Multifaceted role of tensins in cancer

10.7287/peerj.preprints.27990 ◽

2019 ◽

Author(s):

Abdulaziz Alfahed ◽

Teresa P Raposo ◽

Mohammad Ilyas

Keyword(s):

Cancer Biology ◽

Focal Adhesions ◽

Adaptor Proteins ◽

Therapeutic Strategies ◽

Cell Behavior ◽

Surrounding Environment ◽

Signaling Mechanisms ◽

Different Types ◽

Biochemical Signals

Tensins are structural adaptor proteins localized at focal adhesions. Tensins can act as mechanosensors and participate in the transduction of biochemical signals from the extracellular matrix to the cytoskeleton, acting as an interface able to alter cell behavior in responses to changes in their surrounding environment. This review aims to provide a concise summary of the main functions of the four known tensins in cell and cancer biology, their homology and recently unveiled signaling mechanisms. We focus specifically on how tensin 4 (TNS4/Cten) may contribute to cancer both as an oncogene supporting metastasis and as tumour suppressor in different types of tissue. A better understanding of the cancer mechanistics involving tensins may provide the rationale for development of specific therapeutic strategies.

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The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases.

The Journal of Cell Biology ◽

10.1083/jcb.131.6.1857 ◽

1995 ◽

Vol 131 (6) ◽

pp. 1857-1865 ◽

Cited By ~ 266

Author(s):

N A Hotchin ◽

A Hall

Keyword(s):

Extracellular Matrix ◽

Growth Factors ◽

Complex Formation ◽

Map Kinase ◽

Human Fibroblasts ◽

Focal Adhesions ◽

Small Gtpases ◽

Wide Range ◽

Focal Complex ◽

Rho Family

Interaction of cells with extracellular matrix via integrin adhesion receptors plays an important role in a wide range of cellular: functions, for example cell growth, movement, and differentiation. Upon interaction with substrate, integrins cluster and associate with a variety of cytoplasmic proteins to form focal complexes and with the actin cytoskeleton. Although the intracellular signals induced by integrins are at present undefined, it is thought that they are mediated by proteins recruited to the focal complexes. It has been suggested, for example, that after recruitment to focal adhesions p125FAK can activate the ERK1/2 MAP kinase cascade. We have previously reported that members of the rho family of small GTPases can trigger the assembly of focal complexes when activated in cells. Using microinjection techniques, we have now examined the role of the extracellular matrix and of the two GTP-binding proteins, rac and rho, in the assembly of integrin complexes in both mouse and human fibroblasts. We find that the interaction of integrins with extracellular matrix alone is not sufficient to induce integrin clustering and focal complex formation. Similarly, activation of rho or rac by extracellular growth factors does not lead to focal complex formation in the absence of matrix. Focal complexes are only assembled in the presence of both matrix and functionally active members of the rho family. In agreement with this, the interaction of integrins with matrix in the absence of rho/rac activity is unable to activate the ERK1/2 kinases in Swiss 3T3 cells. In fact, ERK1/2 can be activated fully by growth factors in the absence of matrix and it seems unlikely, therefore, that the adhesion dependence of fibroblast growth is mediated through the ras/MAP kinase pathway. We conclude that extracellular matrix is not sufficient to trigger focal complex assembly and subsequent integrin-dependent signal transduction in the absence of functionally active members of the rho family of GTPases.

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BIOMARKERS, NEOANGIOGENESIS AND GROWTH FACTORS IN PANCREATIC CANCER

Research n Practical Medicine Journal ◽

10.17709/2409-2231-2019-6-3-5 ◽

2019 ◽

Vol 6 (3) ◽

pp. 51-64

Author(s):

E. M. Frantsiyants ◽

O. I. Kit ◽

V. I. Aleynov ◽

I. A. Goroshinskaya

Keyword(s):

Pancreatic Cancer ◽

Growth Factors ◽

Growth Factor ◽

Rapid Progression ◽

Therapeutic Effects ◽

Intracellular Signals ◽

Igf I ◽

Key Factor ◽

Endothelial Growth Factor

Pancreatic cancer (PC) is a lethal malignant tumor characterized by a rapid progression, invasiveness and resistance to radiochemotherapy. The development of biomarkers for the early diagnosis of the disease is relevant. Angiogenesis has been identified as a key factor in a number of pathological conditions, including cancer. The proangiogenic signaling molecule – vascular endothelial growth factor (VEGF) and its receptors play a central role in tumor angiogenesis. In this review, we also highlight the dual role of growth factor-β (TGF-β) and touch upon the prospects for therapeutic effects on targets associated with TGF-β signaling in pancreatic cancer. A growing interest is attracted to the role of insulin-like growth factors IGF-I and IGF-II in cancer diseases. IGF-I and its receptor are highly expressed on the surface of pancreatic cancer cell lines that initiate the transduction of intracellular signals associated with the proliferation, invasion and expression of angiogenesis mediators. And so, the study of markers and growth factors may be a new, viable option for the diagnosis and treatment of pancreatic cancer.

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Rab18 regulates focal adhesion dynamics by interacting with kinectin-1 at the endoplasmic reticulum

The Journal of Cell Biology ◽

10.1083/jcb.201809020 ◽

2020 ◽

Vol 219 (7) ◽

Author(s):

Noemi Antonella Guadagno ◽

Azzurra Margiotta ◽

Synne Arstad Bjørnestad ◽

Linda Hofstad Haugen ◽

Ingrid Kjos ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Focal Adhesion ◽

Focal Adhesions ◽

Molecular Switches ◽

Underlying Mechanism ◽

Small Gtpases ◽

Small Gtpase ◽

Canonical Function ◽

Dependent Transport

The members of the Rab family of small GTPases are molecular switches that regulate distinct steps in different membrane traffic pathways. In addition to this canonical function, Rabs can play a role in other processes, such as cell adhesion and motility. Here, we reveal the role of the small GTPase Rab18 as a positive regulator of directional migration in chemotaxis, and the underlying mechanism. We show that knockdown of Rab18 reduces the size of focal adhesions (FAs) and influences their dynamics. Furthermore, we found that Rab18, by directly interacting with the endoplasmic reticulum (ER)-resident protein kinectin-1, controls the anterograde kinesin-1–dependent transport of the ER required for the maturation of nascent FAs and protrusion orientation toward a chemoattractant. Altogether, our data support a model in which Rab18 regulates kinectin-1 transport toward the cell surface to form ER–FA contacts, thus promoting FA growth and cell migration during chemotaxis.

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Multifaceted role of tensins in cancer

10.7287/peerj.preprints.27990v1 ◽

2019 ◽

Author(s):

Abdulaziz Alfahed ◽

Teresa P Raposo ◽

Mohammad Ilyas

Keyword(s):

Cancer Biology ◽

Focal Adhesions ◽

Adaptor Proteins ◽

Therapeutic Strategies ◽

Cell Behavior ◽

Surrounding Environment ◽

Signaling Mechanisms ◽

Different Types ◽

Biochemical Signals

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The Emerging Role of the Insulin-like Growth Factors in Oral Biology

Journal of Dental Research ◽

10.1177/154405910408301102 ◽

2004 ◽

Vol 83 (11) ◽

pp. 832-836 ◽

Cited By ~ 44

Author(s):

H. Werner ◽

J. Katz

Keyword(s):

Growth Factors ◽

Igf System ◽

Pathological Conditions ◽

Tissue Healing ◽

System Components ◽

Igf I ◽

Key Factor ◽

Oral Malignancies ◽

Insulin Like Growth Factors

The insulin-like growth factors (IGF) are a family of growth factors, receptors and binding proteins that are involved in numerous growth and differentiation processes, as well as in various pathological conditions. The aim of this review is to summarize data that has been accumulating in recent years linking the IGF system to a number of physiological and pathological oral processes. The IGF system fulfills an important role in growth and development of teeth, mandible, maxillae, and tongue. It has been postulated that IGF-I may be of great value in the treatment of periodontal defects and in tissue healing. Furthermore, IGF-II has been shown to be overexpressed in salivary gland adenomas, suggesting that aberrant IGF signaling may be a key factor in the etiology of oral malignancies. Understanding the role and regulation of IGF system components in salivary glands and other oral structures will be of significant basic and clinical relevance.

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Extracellular matrix: the gatekeeper of tumor angiogenesis

Biochemical Society Transactions ◽

10.1042/bst20190653 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1543-1555 ◽

Cited By ~ 10

Author(s):

Maurizio Mongiat ◽

Simone Buraschi ◽

Eva Andreuzzi ◽

Thomas Neill ◽

Renato V. Iozzo

Keyword(s):

Extracellular Matrix ◽

Tumor Angiogenesis ◽

Signaling Cascades ◽

Cancer Growth ◽

Cell Behavior ◽

Metastatic Progression ◽

Surface Receptors ◽

The Matrix ◽

Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

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