scholarly journals Ferroptosis-mediated Crosstalk in the Tumor Microenvironment Implicated in Cancer Progression and Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yini Liu ◽  
Chunyan Duan ◽  
Rongyang Dai ◽  
Yi Zeng
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Lipid Peroxides ◽  
Antioxidant Systems ◽  
Biological Processes ◽  
The Novel ◽  
Regulated Cell Death ◽  
Novel Therapeutic Strategies

Ferroptosis is a recently recognized form of non-apoptotic regulated cell death and usually driven by iron-dependent lipid peroxidation and has arisen to play a significant role in cancer biology. Distinct from other types of cell death in morphology, genetics, and biochemistry, ferroptosis is characterized by the accumulation of lipid peroxides and lethal reactive oxygen species controlled by integrated oxidant and antioxidant systems. Increasing evidence indicates that a variety of biological processes, including amino acid, iron, lactate, and lipid metabolism, as well as glutathione, phospholipids, NADPH, and coenzyme Q10 biosynthesis, are closely related to ferroptosis sensitivity. Abnormal ferroptotic response may modulate cancer progression by reprogramming the tumor microenvironment (TME). The TME is widely associated with tumor occurrence because it is the carrier of tumor cells, which interacts with surrounding cells through the circulatory and the lymphatic system, thus influencing the development and progression of cancer. Furthermore, the metabolism processes play roles in maintaining the homeostasis and evolution of the TME. Here, this review focuses on the ferroptosis-mediated crosstalk in the TME, as well as discussing the novel therapeutic strategies for cancer treatment.

scholarly journals The Emerging Role of GC-MSCs in the Gastric Cancer Microenvironment: From Tumor to Tumor Immunity

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zhaoji Pan ◽  
Yiqing Tian ◽  
Guoping Niu ◽  
Chengsong Cao
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Wound Repair ◽  
Critical Role ◽  
The Novel ◽  
Potential Biomarker ◽  
Underlying Mechanisms ◽  
Gastric Cancer Progression

Mesenchymal stem cells (MSCs) have been declared to not only participate in wound repair but also affect tumor progression. Tumor-associated MSCs, directly existing in the tumor microenvironment, play a critical role in tumor initiation, progression, and development. And different tumor-derived MSCs have their own unique characteristics. In this review, we mainly describe and discuss recent advances in our understanding of the emerging role of gastric cancer-derived MSC-like cells (GC-MSCs) in regulating gastric cancer progression and development, as well as the bidirectional influence between GC-MSCs and immune cells of the tumor microenvironment. Moreover, we also discuss the potential biomarker and therapeutic role of GC-MSCs. It is anticipated that new and deep insights into the functionality of GC-MSCs and the underlying mechanisms will promote the novel and promising therapeutic strategies against gastric cancer.

scholarly journals Biological mechanisms linked to inflammation in cancer: Discovery of tumor microenvironment-related biomarkers and their clinical application in solid tumors

2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 8-11 ◽  
Author(s):  
Paola Nisticò ◽  
Gennaro Ciliberto
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Tumor Development ◽  
Short Paper ◽  
Great Relevance ◽  
Cellular Components ◽  
The Relationship

Our view of cancer biology radically shifted from a “cancer-cell-centric” vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved.

scholarly journals Mitochondrial regulation of ferroptosis

2021 ◽  
Vol 220 (9) ◽  
Author(s):  
Boyi Gan
Keyword(s):  
Cell Death ◽  
Cell Biology ◽  
Lipid Peroxides ◽  
Disease Treatment ◽  
Mitochondrial Regulation ◽  
Defense Systems ◽  
Regulated Cell Death ◽  
Mitochondrial Lipid ◽  
Mitochondria Functions ◽  
New Evidence

Ferroptosis is a form of iron-dependent regulated cell death driven by uncontrolled lipid peroxidation. Mitochondria are double-membrane organelles that have essential roles in energy production, cellular metabolism, and cell death regulation. However, their role in ferroptosis has been unclear and somewhat controversial. In this Perspective, I summarize the diverse metabolic processes in mitochondria that actively drive ferroptosis, discuss recently discovered mitochondria-localized defense systems that detoxify mitochondrial lipid peroxides and protect against ferroptosis, present new evidence for the roles of mitochondria in regulating ferroptosis, and outline outstanding questions on this fascinating topic for future investigations. An in-depth understanding of mitochondria functions in ferroptosis will have important implications for both fundamental cell biology and disease treatment.

scholarly journals Ferroptosis and Its Multifaceted Roles in Cerebral Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Yongfa Zhang ◽  
Xiaoyang Lu ◽  
Bai Tai ◽  
Weijia Li ◽  
Tao Li
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Iron Overload ◽  
Hemorrhagic Stroke ◽  
Lipid Peroxides ◽  
Cerebral Stroke ◽  
Intracellular Iron ◽  
Biological Features ◽  
Pathophysiological Process ◽  
Regulated Cell Death

Ferroptosis is a unique regulated cell death defined by the intracellular iron overload and distinct biological features compared with other well-known programmed cell death. Ferroptosis can be triggered by many causes including decreased expression of glutathione (GSH), inhibition of the function of glutathione-dependent peroxidase 4 (GPX4), and system xc–, all of which finally lead to the over-accumulation of lipid peroxides in the cell. Ferroptosis has been reported to play an important role in the pathophysiological process of various cancers. In recent years, much evidence also proved that ferroptosis is involved in the progress of cerebral stroke. In this review, we summarized the characteristics of ferroptosis and the potential relationship between ferroptosis and ischemic and hemorrhagic stroke, to provide new targets and ideas for the therapy of stroke.

scholarly journals Correlation between Oxidative Stress and Transforming Growth Factor-Beta in Cancers

2021 ◽  
Vol 22 (24) ◽  
pp. 13181
Author(s):  
Jinwook Chung ◽  
Md Nazmul Huda ◽  
Yoonhwa Shin ◽  
Sunhee Han ◽  
Salima Akter ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Antioxidant Systems ◽  
Growth Factor Beta

The downregulation of reactive oxygen species (ROS) facilitates precancerous tumor development, even though increasing the level of ROS can promote metastasis. The transforming growth factor-beta (TGF-β) signaling pathway plays an anti-tumorigenic role in the initial stages of cancer development but a pro-tumorigenic role in later stages that fosters cancer metastasis. TGF-β can regulate the production of ROS unambiguously or downregulate antioxidant systems. ROS can influence TGF-β signaling by enhancing its expression and activation. Thus, TGF-β signaling and ROS might significantly coordinate cellular processes that cancer cells employ to expedite their malignancy. In cancer cells, interplay between oxidative stress and TGF-β is critical for tumorigenesis and cancer progression. Thus, both TGF-β and ROS can develop a robust relationship in cancer cells to augment their malignancy. This review focuses on the appropriate interpretation of this crosstalk between TGF-β and oxidative stress in cancer, exposing new potential approaches in cancer biology.

scholarly journals Linking Tumor Microenvironment to Plasticity of Cancer Stem Cells: Mechanisms and Application in Cancer Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaobo Zheng ◽  
Chune Yu ◽  
Mingqing Xu
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Immune Escape ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies ◽  
And Function ◽  
The Relationship

Cancer stem cells (CSCs) are a minority subset of cancer cells that can drive tumor initiation, promote tumor progression, and induce drug resistance. CSCs are difficult to eliminate by conventional therapies and eventually mediate tumor relapse and metastasis. Moreover, recent studies have shown that CSCs display plasticity that renders them to alter their phenotype and function. Consequently, the varied phenotypes result in varied tumorigenesis, dissemination, and drug-resistance potential, thereby adding to the complexity of tumor heterogeneity and further challenging clinical management of cancers. In recent years, tumor microenvironment (TME) has become a hotspot in cancer research owing to its successful application in clinical tumor immunotherapy. Notably, emerging evidence shows that the TME is involved in regulating CSC plasticity. TME can activate stemness pathways and promote immune escape through cytokines and exosomes secreted by immune cells or stromal cells, thereby inducing non-CSCs to acquire CSC properties and increasing CSC plasticity. However, the relationship between TME and plasticity of CSCs remains poorly understood. In this review, we discuss the emerging investigations on TME and CSC plasticity to illustrate the underlying mechanisms and potential implications in suppressing cancer progression and drug resistance. We consider that this review can help develop novel therapeutic strategies by taking into account the interlink between TME and CSC plasticity.

scholarly journals The Status of p53 Oligomeric and Aggregation States in Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 548 ◽  
Author(s):  
Guilherme A. P. de Oliveira ◽  
Elaine C. Petronilho ◽  
Murilo M. Pedrote ◽  
Mayra A. Marques ◽  
Tuane C. R. G. Vieira ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cancer Biology ◽  
Mutant P53 ◽  
Binding Properties ◽  
Research Directions ◽  
The Status ◽  
Multiple Levels ◽  
Novel Therapeutic Strategies ◽  
The Guardian ◽  
Dna Binding Properties

Despite being referred to as the guardian of the genome, when impacted by mutations, p53 can lose its protective functions and become a renegade. The malignant transformation of p53 occurs on multiple levels, such as altered DNA binding properties, acquisition of novel cellular partners, or associating into different oligomeric states. The consequences of these transformations can be catastrophic. Ongoing studies have implicated different oligomeric p53 species as having a central role in cancer biology; however, the correlation between p53 oligomerization status and oncogenic activities in cancer progression remains an open conundrum. In this review, we summarize the roles of different p53 oligomeric states in cancer and discuss potential research directions for overcoming aberrant p53 function associated with them. We address how misfolding and prion-like amyloid aggregation of p53 seem to play a crucial role in cancer development. The misfolded and aggregated states of mutant p53 are prospective targets for the development of novel therapeutic strategies against tumoral diseases.

scholarly journals Biological Functions of Gasdermins in Cancer: From Molecular Mechanisms to Therapeutic Potential

2021 ◽  
Vol 9 ◽  
Author(s):  
Man Wang ◽  
Xinzhe Chen ◽  
Yuan Zhang
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Effector Proteins ◽  
Biological Functions ◽  
Cancer Cell Growth ◽  
Cancer Pathogenesis

Pyroptosis is a type of lytic programmed cell death triggered by various inflammasomes that sense danger signals. Pyroptosis has recently attracted great attention owing to its contributory role in cancer. Pyroptosis plays an important role in cancer progression by inducing cancer cell death or eliciting anticancer immunity. The participation of gasdermins (GSDMs) in pyroptosis is a noteworthy recent discovery. GSDMs have emerged as a group of pore-forming proteins that serve important roles in innate immunity and are composed of GSDMA-E and Pejvakin (PJVK) in human. The N-terminal domains of GSDMs, expect PJVK, can form pores on the cell membrane and function as effector proteins of pyroptosis. Remarkably, it has been found that GSDMs are abnormally expressed in several forms of cancers. Moreover, GSDMs are involved in cancer cell growth, invasion, metastasis and chemoresistance. Additionally, increasing evidence has indicated an association between GSDMs and clinicopathological features in cancer patients. These findings suggest the feasibility of using GSDMs as prospective biomarkers for cancer diagnosis, therapeutic intervention and prognosis. Here, we review the progress in unveiling the characteristics and biological functions of GSDMs. We also focus on the implication and molecular mechanisms of GSDMs in cancer pathogenesis. Investigating the relationship between GSDMs and cancer biology could assist us to explore new therapeutic avenues for cancer prevention and treatment.

scholarly journals Ferroptosis: Biochemistry and Biology in Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhiyuan Shi ◽  
Lei Zhang ◽  
Jianzhong Zheng ◽  
Huimin Sun ◽  
Chen Shao
Keyword(s):  
Cancer Cells ◽  
Acid Metabolism ◽  
Cancer Therapeutics ◽  
Lipid Peroxides ◽  
Glutathione Metabolism ◽  
Biological Processes ◽  
Regulated Cell Death ◽  
Clinical Strategies ◽  
Dependent Form ◽  
Anti Tumor Activity

The challenge of eradicating cancer is that cancer cells possess diverse mechanisms to protect themselves from clinical strategies. Recently, ferroptosis has been shown to exhibit appreciable anti-tumor activity that could be harnessed for cancer therapy in the future. Ferroptosis is an iron-dependent form of regulated cell death that is characterized by the oxidization of polyunsaturated fatty acids (PUFAs) and accumulation of lipid peroxides. Ferroptosis has been closely correlated with numerous biological processes, such as amino acid metabolism, glutathione metabolism, iron metabolism, and lipid metabolism, as well as key regulators including GPX4, FSP1, NRF2, and p53. Although ferroptosis could be involved in killing various cancer cells, multiple aspects of this phenomenon remain unresolved. In this review, we summarize the biochemistry and biology of ferroptosis in diverse cancers and discuss the potential mechanisms of ferroptosis, which might pave the way for guiding cancer therapeutics.

scholarly journals Ferroptosis: A New Promising Target for Lung Cancer Therapy

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Rui Xiong ◽  
Ruyuan He ◽  
Bohao Liu ◽  
Wenyang Jiang ◽  
Bo Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Lipid Peroxides ◽  
Cancer Therapies ◽  
Biological Processes ◽  
Promising Target ◽  
Underlying Basis ◽  
Lung Cancer Therapy ◽  
New Type ◽  
Growth Of Tumor

Ferroptosis is a new type of regulatory cell death that differs from autophagy, apoptosis, necrosis, and pyroptosis; it is caused primarily by the accumulation of iron and lipid peroxides in the cell. Studies have shown that many classical signaling pathways and biological processes are involved in the process of ferroptosis. In recent years, investigations have revealed that ferroptosis plays a crucial role in the progression of tumors, especially lung cancer. In particular, inducing ferroptosis in cells can inhibit the growth of tumor cells, thereby reversing tumorigenesis. In this review, we summarize the characteristics of ferroptosis from its underlying basis and role in lung cancer and provide possible applications for it in lung cancer therapies.

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