scholarly journals The Role of Decorin and Biglycan Signaling in Tumorigenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Valentina Diehl ◽  
Lisa Sophie Huber ◽  
Jonel Trebicka ◽  
Malgorzata Wygrecka ◽  
Renato V. Iozzo ◽  
...  
Keyword(s):  
Tumor Biology ◽  
Malignant Neoplasm ◽  
Cancer Development ◽  
Structural Homology ◽  
Therapeutic Implications ◽  
Surface Receptors ◽  
Distinct Cell ◽  
Adaptive Nature ◽  
Novel Therapeutic

The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer development. In this review, we summarize growing evidence for the complex roles of decorin and biglycan signaling in tumor biology and address potential novel therapeutic implications.

scholarly journals The Role of Alternative Lengthening of Telomeres Mechanism in Cancer: Translational and Therapeutic Implications

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 949 ◽  
Author(s):  
Marta Recagni ◽  
Joanna Bidzinska ◽  
Nadia Zaffaroni ◽  
Marco Folini
Keyword(s):  
Cancer Cells ◽  
Tumor Biology ◽  
Telomerase Activity ◽  
Telomere Maintenance ◽  
Limited Information ◽  
Adaptive Responses ◽  
Therapeutic Implications ◽  
Telomerase Inhibitors ◽  
Alternative Lengthening

Telomere maintenance mechanisms (i.e., telomerase activity (TA) and the alternative lengthening of telomere (ALT) mechanism) contribute to tumorigenesis by providing unlimited proliferative capacity to cancer cells. Although the role of either telomere maintenance mechanisms seems to be equivalent in providing a limitless proliferative ability to tumor cells, the contribution of TA and ALT to the clinical outcome of patients may differ prominently. In addition, several strategies have been developed to interfere with TA in cancer, including Imetelstat that has been the first telomerase inhibitor tested in clinical trials. Conversely, the limited information available on the molecular underpinnings of ALT has hindered thus far the development of genuine ALT-targeting agents. Moreover, whether anti-telomerase therapies may be hampered or not by possible adaptive responses is still debatable. Nonetheless, it is plausible hypothesizing that treatment with telomerase inhibitors may exert selective pressure for the emergence of cancer cells that become resistant to treatment by activating the ALT mechanism. This notion, together with the evidence that both telomere maintenance mechanisms may coexist within the same tumor and may distinctly impinge on patients’ outcomes, suggests that ALT may exert an unexpected role in tumor biology that still needs to be fully elucidated.

scholarly journals The role of glycogen synthase kinase 3 (GSK3) in cancer with emphasis on ovarian cancer development and progression: A comprehensive review

2020 ◽  
Author(s):  
Mislav Glibo ◽  
Alan Serman ◽  
Valentina Karin-Kujundzic ◽  
Ivanka Bekavac Vlatkovic ◽  
Berivoj Miskovic ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Glycogen Synthase ◽  
Alpha Helix ◽  
Glycogen Synthase Kinase ◽  
Cancer Development ◽  
Glycogen Synthase Kinase 3 ◽  
Serine Threonine Kinase ◽  
Therapeutic Implications ◽  
Cellular Processes

Glycogen synthase kinase 3 (GSK3) is a monomeric serine-threonine kinase discovered in 1980 in a rat skeletal muscle. It has been involved in various cellular processes including embryogenesis, immune response, inflammation, apoptosis, autophagy, wound healing, neurodegeneration and carcinogenesis. GSK3 exists in two different isoforms, GSK3α and GSK3β, both containing seven antiparallel beta-plates, a short linking part and an alpha helix, but coded by different genes and variously expressed in human tissues. In the current review, we comprehensively appraise the current literature on the role of GSK3 in various cancers with emphasis on ovarian carcinoma. Our findings indicate that the role of GSK3 in ovarian cancer development cannot be decisively determined as the currently available data support both prooncogenic and tumor-suppressive effects. Likewise, the clinical impact of GSK3 expression on ovarian cancer patients and its potential therapeutic implications are also limited. Further studies are needed to fully elucidate the pathophysiological and clinical implications of GSK3 activity in ovarian cancer.

scholarly journals The Pivotal Role of the Dysregulation of Cholesterol Homeostasis in Cancer: Implications for Therapeutic Targets

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1410 ◽  
Author(s):  
Etienne Ho Kit Mok ◽  
Terence Kin Wah Lee
Keyword(s):  
Cholesterol Metabolism ◽  
Cholesterol Content ◽  
Epidemiological Studies ◽  
Cholesterol Homeostasis ◽  
Cancer Development ◽  
Therapeutic Implications ◽  
Functional Roles ◽  
Cancer Pathogenesis ◽  
Therapeutic Avenue

Cholesterol plays an important role in cellular homeostasis by maintaining the rigidity of cell membranes, providing a medium for signaling transduction, and being converted into other vital macromolecules, such as sterol hormones and bile acids. Epidemiological studies have shown the correlation between cholesterol content and cancer incidence worldwide. Accumulating evidence has shown the emerging roles of the dysregulation of cholesterol metabolism in cancer development. More specifically, recent reports have shown the distinct role of cholesterol in the suppression of immune cells, regulation of cell survival, and modulation of cancer stem cells in cancer. Here, we provide a comprehensive review of the epidemiological analysis, functional roles, and mechanistic action of cholesterol homeostasis in regard to its contribution to cancer development. Based on the existing data, cholesterol homeostasis is identified to be a new key player in cancer pathogenesis. Lastly, we also discuss the therapeutic implications of natural compounds and cholesterol-lowering drugs in cancer prevention and treatment. In conclusion, intervention in cholesterol metabolism may offer a new therapeutic avenue for cancer treatment.

scholarly journals The emerging role of WWP1 in cancer development and progression

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaoli Hu ◽  
Jiangtao Yu ◽  
Zixia Lin ◽  
Renqian Feng ◽  
Zhi-wei Wang ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cancer Patients ◽  
Clinical Features ◽  
Therapeutic Strategies ◽  
Review Article ◽  
Cancer Development ◽  
Ubiquitin Protein Ligase ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

AbstractEmerging evidence demonstrates that WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) participates into carcinogenesis and tumor progression. In this review article, we will describe the association between dysregulated WWP1 expression and clinical features of cancer patients. Moreover, we summarize the both oncogenic and tumor suppressive functions of WWP1 in a variety of human cancers. Furthermore, we briefly describe the downstream substrates of WWP1 and its upstream factors to regulate the expression of WWP1. Notably, targeting WWP1 by its inhibitors or natural compounds is potentially useful for treating human malignancies. Finally, we provide the perspectives regarding WWP1 in cancer development and therapies. We hope this review can stimulate the research to improve our understanding of WWP1-mediated tumorigenesis and accelerate the discovery of novel therapeutic strategies via targeting WWP1 expression in cancers.

scholarly journals Molecular Alterations in Thyroid Cancer: From Bench to Clinical Practice

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 709 ◽  
Author(s):  
Elena Tirrò ◽  
Federica Martorana ◽  
Chiara Romano ◽  
Silvia Rita Vitale ◽  
Gianmarco Motta ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Tumor Biology ◽  
Cancer Development ◽  
Disease Evolution ◽  
Molecular Alterations ◽  
Genomic Landscape ◽  
Thyroid Malignancies

Thyroid cancer comprises different clinical and histological entities. Whereas differentiated (DTCs) malignancies are sensitive to radioiodine therapy, anaplastic (ATCs) and medullary (MTCs) tumors do not uptake radioactive iodine and display aggressive features associated with a poor prognosis. Moreover, in a majority of DTCs, disease evolution leads to the progressive loss of iodine sensitivity. Hence, iodine-refractory DTCs, along with ATCs and MTCs, require alternative treatments reflective of their different tumor biology. In the last decade, the molecular mechanisms promoting thyroid cancer development and progression have been extensively studied. This has led to a better understanding of the genomic landscape, displayed by thyroid malignancies, and to the identification of novel therapeutic targets. Indeed, several pharmacological compounds have been developed for iodine-refractory tumors, with four multi-target tyrosine kinase inhibitors already available for DTCs (sorafenib and lenvatinib) and MTCs (cabozantib and vandetanib), and a plethora of drugs currently being evaluated in clinical trials. In this review, we will describe the genomic alterations and biological processes intertwined with thyroid cancer development, also providing a thorough overview of targeted drugs already tested or under investigation for these tumors. Furthermore, given the existing preclinical evidence, we will briefly discuss the potential role of immunotherapy as an additional therapeutic strategy for the treatment of thyroid cancer.

scholarly journals The Microenvironment of Pituitary Tumors—Biological and Therapeutic Implications

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1605 ◽  
Author(s):  
Mirela Diana Ilie ◽  
Alexandre Vasiljevic ◽  
Gérald Raverot ◽  
Philippe Bertolino
Keyword(s):  
Extracellular Matrix ◽  
Therapeutic Target ◽  
Pituitary Tumor ◽  
Current Knowledge ◽  
Tumor Biology ◽  
Pituitary Tumors ◽  
Human Pituitary ◽  
Therapeutic Implications ◽  
Extracellular Matrix Components

The tumor microenvironment (TME) includes resident and infiltrative non-tumor cells, as well as blood and lymph vessels, extracellular matrix molecules, and numerous soluble factors, such as cytokines and chemokines. While the TME is now considered to be a prognostic tool and a therapeutic target for many cancers, little is known about its composition in pituitary tumors. This review summarizes our current knowledge of the TME within pituitary tumors and the strong interest in TME as a therapeutic target. While we cover the importance of angiogenesis and immune infiltrating cells, we also address the role of the elusive folliculostellate cells, the emerging literature on pituitary tumor-associated fibroblasts, and the contribution of extracellular matrix components in these tumors. The cases of human pituitary tumors treated with TME-targeting therapies are reviewed and emerging concepts of vascular normalization and combined therapies are presented. Together, this snapshot overview of the current literature pinpoints not only the underestimated role of TME components in pituitary tumor biology, but also the major promise it may offer for both prognosis and targeted therapeutics.

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
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.

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

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