scholarly journals Sweetening the hallmarks of cancer: Galectins as multifunctional mediators of tumor progression

2019 ◽  
Vol 217 (2) ◽  
Author(s):  
María Romina Girotti ◽  
Mariana Salatino ◽  
Tomás Dalotto-Moreno ◽  
Gabriel A. Rabinovich
Keyword(s):  
Immune Responses ◽  
Tumor Progression ◽  
Stromal Cells ◽  
Human Cancer ◽  
Invasion And Metastasis ◽  
Hallmarks Of Cancer ◽  
Evolutionarily Conserved ◽  
Proliferative Signaling ◽  
Organizing Principles

Hanahan and Weinberg have proposed 10 organizing principles that enable growth and metastatic dissemination of cancer cells. These distinctive and complementary capabilities, defined as the “hallmarks of cancer,” include the ability of tumor cells and their microenvironment to sustain proliferative signaling, evade growth suppressors, resist cell death, promote replicative immortality, induce angiogenesis, support invasion and metastasis, reprogram energy metabolism, induce genomic instability and inflammation, and trigger evasion of immune responses. These common features are hierarchically regulated through different mechanisms, including those involving glycosylation-dependent programs that influence the biological and clinical impact of each hallmark. Galectins, an evolutionarily conserved family of glycan-binding proteins, have broad influence in tumor progression by rewiring intracellular and extracellular circuits either in cancer or stromal cells, including immune cells, endothelial cells, and fibroblasts. In this review, we dissect the role of galectins in shaping cellular circuitries governing each hallmark of tumors, illustrating relevant examples and highlighting novel opportunities for treating human cancer.

scholarly journals Versican and Versican-matrikines in Cancer Progression, Inflammation, and Immunity

2020 ◽  
Vol 68 (12) ◽  
pp. 871-885 ◽  
Author(s):  
Athanasios Papadas ◽  
Garrett Arauz ◽  
Alexander Cicala ◽  
Joshua Wiesner ◽  
Fotis Asimakopoulos
Keyword(s):  
Immune Responses ◽  
Cancer Progression ◽  
Immune Cell ◽  
Invasion And Metastasis ◽  
Tissue Invasion ◽  
Immune Biomarkers ◽  
Cancer Inflammation ◽  
Proliferative Signaling ◽  
Growth Suppressor

Versican is an extracellular matrix proteoglycan with key roles in multiple facets of cancer development, ranging from proliferative signaling, evasion of growth-suppressor pathways, regulation of cell death, promotion of neoangiogenesis, and tissue invasion and metastasis. Multiple lines of evidence implicate versican and its bioactive proteolytic fragments (matrikines) in the regulation of cancer inflammation and antitumor immune responses. The understanding of the dynamics of versican deposition/accumulation and its proteolytic turnover holds potential for the development of novel immune biomarkers as well as approaches to reset the immune thermostat of tumors, thus promoting efficacy of modern immunotherapies. This article summarizes work from several laboratories, including ours, on the role of this central matrix proteoglycan in tumor progression as well as tumor-immune cell cross-talk:

scholarly journals Returning to the Hallmarks of Cancer: A Brief Review and Revision

2021 ◽  
Vol 9 (2) ◽  
pp. 01-06
Author(s):  
Kaushalendra Mani Tripathi
Keyword(s):  
Drug Resistance ◽  
Genome Instability ◽  
Invasion And Metastasis ◽  
Hallmarks Of Cancer ◽  
Different Types ◽  
Cellular Energetics ◽  
Immune Destruction ◽  
Near Future ◽  
Proliferative Signaling

The hallmarks of cancer represent principals and mechanisms on which, different types of cancers function and proliferate, These principals which also include the revised edition include sustained proliferative signaling, Evading growth suppressors , avoiding immune destruction, enabling replicative immortality, tumor promoting inflammation, activating invasion and metastasis, Inducing angiogenesis, genome instability and mutation, resisting cell death, deregulating cellular energetics. This article reviews these hallmarks and suggests any additional hallmark that can be further investigated and integrated into the revised edition , Hanahan and Weinberg’s hallmark of cancer are great pillars of understanding for modern cancer study and are open to modification , making it easily approachable ,critiqued and adds the possibility of additions in the near future. The role of exosomes are discussed with the potential to categorize drug resistance as a separate hallmark to assist us in developing therapeutics that can counter or bypass these mechanisms that assist cancer cells to proliferate even further.

scholarly journals ASCT2 and LAT1 Contribution to the Hallmarks of Cancer: From a Molecular Perspective to Clinical Translation

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 203
Author(s):  
Catarina Lopes ◽  
Carina Pereira ◽  
Rui Medeiros
Keyword(s):  
Phase 1 ◽  
Clinical Applications ◽  
Selective Inhibitor ◽  
Cancer Prognosis ◽  
Amino Acid Transporters ◽  
Invasion And Metastasis ◽  
Hallmarks Of Cancer ◽  
Cellular Energetics ◽  
Proliferative Signaling

The role of the amino acid transporters ASCT2 and LAT1 in cancer has been explored throughout the years. In this review, we report their impact on the hallmarks of cancer, as well as their clinical significance. Overall, both proteins have been associated with cell death resistance through dysregulation of caspases and sustainment of proliferative signaling through mTOR activation. Furthermore, ASCT2 appears to play an important role in cellular energetics regulation, whereas LAT1 expression is associated with angiogenesis and invasion and metastasis activation. The molecular impact of these proteins on the hallmarks of cancer translates into various clinical applications and both transporters have been identified as prognostic factors in many types of cancer. Concerning their role as therapeutic targets, efforts have been undertaken to synthesize competitive or irreversible ASCT2 and LAT1 inhibitors. However, JHP203, a selective inhibitor of the latter, is, to the best of our knowledge, the only compound included in a Phase 1 clinical trial. In conclusion, considering the usefulness of ASCT2 and LAT1 in a variety of cancer-related pathways and cancer therapy/diagnosis, the development and testing of novel inhibitors for these transporters that could be evaluated in clinical trials represents a promising approach to cancer prognosis improvement.

scholarly journals Epithelial-mesenchymal plasticity: How have quantitative mathematical models helped improve our understanding?

2017 ◽  
Author(s):  
Mohit Kumar Jolly ◽  
Satyendra C Tripathi ◽  
Jason A Somarelli ◽  
Samir M Hanash ◽  
Herbert Levine
Keyword(s):  
Phenotypic Plasticity ◽  
Mathematical Models ◽  
Tumor Progression ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Invasion And Metastasis ◽  
Hallmarks Of Cancer ◽  
Mesenchymal Phenotype ◽  
Extracellular Signals ◽  
Clinical Challenge

AbstractPhenotypic plasticity, the ability of cells to reversibly alter their phenotypes in response to signals, presents a significant clinical challenge to treating solid tumors. Tumor cells utilize phenotypic plasticity to evade therapies, metastasize, and colonize distant organs. As a result, phenotypic plasticity can accelerate tumor progression. A well-studied example of phenotypic plasticity is the bidirectional conversions among epithelial, mesenchymal, and hybrid epithelial/mesenchymal phenotype(s). These conversions can alter a repertoire of cellular traits associated with multiple hallmarks of cancer, such as metabolism, immune-evasion, and invasion and metastasis. To tackle the complexity and heterogeneity of these transitions, mathematical models have been developed that seek to capture the experimentally-verified molecular mechanisms and act as ‘ hypothesis-generating machines’. Here, we discuss how these quantitative mathematical models have helped us explain existing experimental data, guided further experiments, and provided an improved conceptual framework for understanding how multiple intracellular and extracellular signals can drive epithelial-mesenchymal plasticity at both the single-cell and population levels. We also discuss the implications of this plasticity in driving multiple aggressive facets of tumor progression.

scholarly journals A Different Facet of p53 Function: Regulation of Immunity and Inflammation During Tumor Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Di Shi ◽  
Peng Jiang
Keyword(s):  
Tumor Suppressor ◽  
Immune Responses ◽  
Tumor Development ◽  
Suppressive Effect ◽  
Innate Immune ◽  
Tumor Suppressor P53 ◽  
Cycle Arrest ◽  
Evolutionarily Conserved ◽  
Cellular Stresses

As a key transcription factor, the evolutionarily conserved tumor suppressor p53 (encoded by TP53) plays a central role in response to various cellular stresses. A variety of biological processes are regulated by p53 such as cell cycle arrest, apoptosis, senescence and metabolism. Besides these well-known roles of p53, accumulating evidence show that p53 also regulates innate immune and adaptive immune responses. p53 influences the innate immune system by secreted factors that modulate macrophage function to suppress tumourigenesis. Dysfunction of p53 in cancer affects the activity and recruitment of T and myeloid cells, resulting in immune evasion. p53 can also activate key regulators in immune signaling pathways which support or impede tumor development. Hence, it seems that the tumor suppressor p53 exerts its tumor suppressive effect to a considerable extent by modulating the immune response. In this review, we concisely discuss the emerging connections between p53 and immune responses, and their impact on tumor progression. Understanding the role of p53 in regulation of immunity will help to developing more effective anti-tumor immunotherapies for patients with TP53 mutation or depletion.

scholarly journals Reprogramming Interferon Regulatory Factor Signaling in Cardiometabolic Diseases

Physiology ◽  
2017 ◽  
Vol 32 (3) ◽  
pp. 210-223 ◽  
Author(s):  
Yaxing Zhang ◽  
Hongliang Li
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Immune Cells ◽  
Interferon Regulatory Factor ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Regulatory Factor ◽  
Cardiometabolic Diseases ◽  
Evolutionarily Conserved

Interferon regulatory factors (IRFs) are evolutionarily conserved proteins expressed not only in immune cells but also in other tissues and organs outside the immune system. In this review, we discuss mechanisms responsible for IRF-mediated innate immune responses and the function and mechanism of IRFs in cardiometabolic diseases. We focus on the role of IRFs in innate immunity and cardiometabolic homeostasis, and highlight reprogrammed IRF signaling.

scholarly journals Structural Insights into the Evolutionarily Conserved BAF Chromatin Remodeling Complex

Biology ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 146
Author(s):  
Ryan D. Marcum ◽  
Alexis A. Reyes ◽  
Yuan He
Keyword(s):  
High Frequency ◽  
Human Cancer ◽  
Chromatin Accessibility ◽  
Baf Complex ◽  
Cellular Processes ◽  
Chromatin Remodeling Complex ◽  
Evolutionarily Conserved ◽  
Potential Impact ◽  
Structural Insights

The switch/sucrose nonfermentable (SWI/SNF) family of proteins acts to regulate chromatin accessibility and plays an essential role in multiple cellular processes. A high frequency of mutations has been found in SWI/SNF family subunits by exome sequencing in human cancer, and multiple studies support its role in tumor suppression. Recent structural studies of yeast SWI/SNF and its human homolog, BAF (BRG1/BRM associated factor), have provided a model for their complex assembly and their interaction with nucleosomal substrates, revealing the molecular function of individual subunits as well as the potential impact of cancer-associated mutations on the remodeling function. Here we review the structural conservation between yeast SWI/SNF and BAF and examine the role of highly mutated subunits within the BAF complex.

Exploring the role of endothelium in the tumour response to anti-angiogenic therapy

2014 ◽  
Vol 42 (6) ◽  
pp. 1569-1575 ◽  
Author(s):  
Yi-Chao He ◽  
Michael M. Halford ◽  
Marc G. Achen ◽  
Steven A. Stacker
Keyword(s):  
Human Cancer ◽  
Tumour Response ◽  
Tumour Microenvironment ◽  
Hallmarks Of Cancer ◽  
Patient Response ◽  
Angiogenic Therapy ◽  
Wide Range ◽  
Cancer Inhibition ◽  
Insight Into

A chronic hyperactivated angiogenic state in cancer plays an important role in tumour growth and metastasis and has been identified as one of the hallmarks of cancer. Inhibition of this process has been associated with tumour suppression in many pre-clinical contexts using different animal tumour models. Anti-angiogenic therapeutics were subsequently developed and used to treat several prevalent types of human cancer. However, recent clinical experience has revealed limitations of this approach in treating cancer as patient response varies over a wide range. Given that there are complex underlying molecular and cellular changes provoked by anti-angiogenic treatment within the tumour microenvironment (TME), it is not surprising that modest effectiveness and resistance have been observed in the clinical setting. This article discusses these issues in the context of VEGF-A-targeted anti-angiogenic treatment of cancer and provides insight into the importance of tumour endothelium for understanding the tumour response to anti-angiogenic therapy. Special consideration is also given to possible approaches for investigating how endothelium contributes to the tumour response to anti-angiogenic agents and for exploring the therapeutic and biomarker potential of targeting tumour endothelium.

scholarly journals Lymphoid Tissue Mesenchymal Stromal Cells in Development and Tissue Remodeling

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Luca Genovese ◽  
Andrea Brendolan
Keyword(s):  
Immune Responses ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Activation ◽  
Critical Role ◽  
Tissue Remodeling ◽  
Stromal Microenvironment ◽  
Inflammatory Conditions ◽  
Secondary Lymphoid Organs

Secondary lymphoid organs (SLOs) are sites that facilitate cell-cell interactions required for generating adaptive immune responses. Nonhematopoietic mesenchymal stromal cells have been shown to play a critical role in SLO function, organization, and tissue homeostasis. The stromal microenvironment undergoes profound remodeling to support immune responses. However, chronic inflammatory conditions can promote uncontrolled stromal cell activation and aberrant tissue remodeling including fibrosis, thus leading to tissue damage. Despite recent advancements, the origin and role of mesenchymal stromal cells involved in SLO development and remodeling remain unclear.

Role of Transforming Growth Factor Beta in Human Cancer

2005 ◽  
Vol 23 (9) ◽  
pp. 2078-2093 ◽  
Author(s):  
Rebecca L. Elliott ◽  
Gerard C. Blobe
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Human Cancer ◽  
Inhibition Of Proliferation ◽  
Human Cancers ◽  
Growth Factor Beta

Transforming growth factor beta (TGF-β) is a ubiquitous and essential regulator of cellular and physiologic processes including proliferation, differentiation, migration, cell survival, angiogenesis, and immunosurveillance. Alterations in the TGF-β signaling pathway, including mutation or deletion of members of the signaling pathway and resistance to TGF-β-mediated inhibition of proliferation are frequently observed in human cancers. Although these alterations define a tumor suppressor role for the TGF-β pathway in human cancer, TGF-β also mediates tumor-promoting effects, either through differential effects on tumor and stromal cells or through a fundamental alteration in the TGF-β responsiveness of the tumor cells themselves. TGF-β and members of the TGF-β signaling pathway are being evaluated as prognostic or predictive markers for cancer patients. Ongoing advances in understanding the TGF-β signaling pathway will enable targeting of this pathway for the chemoprevention and treatment of human cancers.

Sign in / Sign up

Export Citation Format

Share Document