scholarly journals Involvement of the FAK Network in Pathologies Related to Altered Mechanotransduction

2020 ◽  
Vol 21 (24) ◽  
pp. 9426
Author(s):  
Enrica Urciuoli ◽  
Barbara Peruzzi
Keyword(s):  
Focal Adhesion ◽  
Gene Mutations ◽  
Living Cells ◽  
Cancer Development ◽  
Muscular Dystrophies ◽  
Matrix Stiffness ◽  
Essential Factor ◽  
Extracellular Matrix Stiffness ◽  
And Function ◽  
Biochemical Signals

Mechanotransduction is a physiological process in which external mechanical stimulations are perceived, interpreted, and translated by cells into biochemical signals. Mechanical stimulations exerted by extracellular matrix stiffness and cell–cell contacts are continuously applied to living cells, thus representing a key pivotal trigger for cell homeostasis, survival, and function, as well as an essential factor for proper organ development and metabolism. Indeed, a deregulation of the mechanotransduction process consequent to gene mutations or altered functions of proteins involved in perceiving cellular and extracellular mechanics can lead to a broad range of diseases, from muscular dystrophies and cardiomyopathies to cancer development and metastatization. Here, we recapitulate the involvement of focal adhesion kinase (FAK) in the cellular conditions deriving from altered mechanotransduction processes.

scholarly journals Functions of the Tumor Suppressors p53 and Rb in Actin Cytoskeleton Remodeling

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Takahiro Ebata ◽  
Hiroaki Hirata ◽  
Keiko Kawauchi
Keyword(s):  
Extracellular Matrix ◽  
Actin Cytoskeleton ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Tumor Suppressors ◽  
Retinoblastoma Protein ◽  
Matrix Stiffness ◽  
Extracellular Matrix Stiffness ◽  
Cytoskeleton Remodeling ◽  
Biochemical Signals

Mechanical microenvironments, such as extracellular matrix stiffness and strain, have crucial roles in cancer progression. Cells sense their microenvironments with mechanosensing biomolecules, which is accompanied by the modulation of actin cytoskeleton structures, and the signals are subsequently transduced downstream as biochemical signals. The tumor suppressors p53 and retinoblastoma protein (Rb) are known to prevent cancer progression. The p53 and Rb signaling pathways are disrupted in many types of cancers. Here, we review recent findings about the roles of these tumor suppressors in the regulation of mechanosensing biomolecules and the actin cytoskeleton. We further discuss how dysfunction in the p53- and/or Rb-mediated mechanosignaling pathways is potentially involved in cancer progression. These pathways might provide good targets for developing anticancer therapies.

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

Focal Adhesion Kinase in Ovarian Cancer: A Potential Therapeutic Target for Platinum and Taxane-Resistant Tumors

2019 ◽  
Vol 19 (3) ◽  
pp. 179-188 ◽  
Author(s):  
Arkene Levy ◽  
Khalid Alhazzani ◽  
Priya Dondapati ◽  
Ali Alaseem ◽  
Khadijah Cheema ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Tumor Stage ◽  
Current Status ◽  
Potential Therapeutic Target ◽  
Resistant Disease ◽  
Development Of Resistance ◽  
And Function ◽  
Mdr 1

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase, which is an essential player in regulating cell migration, invasion, adhesion, proliferation, and survival. Its overexpression and activation have been identified in sixty-eight percent of epithelial ovarian cancer patients and this is significantly associated with higher tumor stage, metastasis, and shorter overall survival of these patients. Most recently, a new role has emerged for FAK in promoting resistance to taxane and platinum-based therapy in ovarian and other cancers. The development of resistance is a complex network of molecular processes that make the identification of a targetable biomarker in platinum and taxane-resistant ovarian cancer a major challenge. FAK overexpression upregulates ALDH and XIAP activity in platinum-resistant and increases CD44, YB1, and MDR-1 activity in taxaneresistant tumors. FAK is therefore now emerging as a prognostically significant candidate in this regard, with mounting evidence from recent successes in preclinical and clinical trials using small molecule FAK inhibitors. This review will summarize the significance and function of FAK in ovarian cancer, and its emerging role in chemotherapeutic resistance. We will discuss the current status of FAK inhibitors in ovarian cancers, their therapeutic competencies and limitations, and further propose that the combination of FAK inhibitors with platinum and taxane-based therapies could be an efficacious approach in chemotherapeutic resistant disease.

scholarly journals Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 359
Author(s):  
Hsiang-Hao Chuang ◽  
Yen-Yi Zhen ◽  
Yu-Chen Tsai ◽  
Cheng-Hao Chuang ◽  
Ming-Shyan Huang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Tumor Suppressors ◽  
Protein Conformation ◽  
Genome Stability ◽  
Recent Progress ◽  
Multiple Roles ◽  
Cancer Development ◽  
Cancer Hallmarks ◽  
Underlying Mechanisms ◽  
And Function

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. In this review, we summarize the underlying mechanisms of Pin1-mediated upregulation of oncogenes and downregulation of tumor suppressors in cancer development. Furthermore, we also discuss the multiple roles of Pin1 in cancer hallmarks and examine Pin1 as a desirable pharmaceutical target for cancer therapy. We also summarize the recent progress of Pin1-targeted small-molecule compounds for anticancer activity.

Intestinal metaplasia in Barrett's oesophagus: An essential factor to predict the risk of dysplasia and cancer development

2016 ◽  
Vol 48 (2) ◽  
pp. 144-147 ◽  
Author(s):  
Marianna Salemme ◽  
Vincenzo Villanacci ◽  
Gianpaolo Cengia ◽  
Renzo Cestari ◽  
Guido Missale ◽  
...  
Keyword(s):  
Intestinal Metaplasia ◽  
Cancer Development ◽  
Barrett’S Oesophagus ◽  
Essential Factor ◽  
Barrett's Oesophagus

scholarly journals In Vivo Role of Focal Adhesion Kinase in Regulating Pancreatic  -Cell Mass and Function Through Insulin Signaling, Actin Dynamics, and Granule Trafficking

Diabetes ◽  
2012 ◽  
Vol 61 (7) ◽  
pp. 1708-1718 ◽  
Author(s):  
E. P. Cai ◽  
M. Casimir ◽  
S. A. Schroer ◽  
C. T. Luk ◽  
S. Y. Shi ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Insulin Signaling ◽  
Cell Mass ◽  
Actin Dynamics ◽  
Pancreatic Cell ◽  
And Function

scholarly journals The Hippo Pathway: A Master Regulatory Network Important in Cancer

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1416
Author(s):  
Qiuping Liu ◽  
Xiaomeng Liu ◽  
Guanbin Song
Keyword(s):  
Metabolic Regulation ◽  
Human Cancer ◽  
Hippo Pathway ◽  
Tumor Development ◽  
Biological Significance ◽  
Cancer Development ◽  
Hippo Signaling ◽  
Complex Regulation ◽  
And Function ◽  
The Hippo Pathway

The Hippo pathway is pervasively activated and has been well recognized to play critical roles in human cancer. The deregulation of Hippo signaling involved in cancer development, progression, and resistance to cancer treatment have been confirmed in several human cancers. Its biological significance and deregulation in cancer have drawn increasing interest in the past few years. A fundamental understanding of the complexity of the Hippo pathway in cancer is crucial for improving future clinical interventions and therapy for cancers. In this review, we try to clarify the complex regulation and function of the Hippo signaling network in cancer development, including its role in signal transduction, metabolic regulation, and tumor development, as well as tumor therapies targeting the Hippo pathway.

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