scholarly journals The Dual-Role of Methylglyoxal in Tumor Progression – Novel Therapeutic Approaches

2021 ◽  
Vol 11 ◽  
Author(s):  
Alessia Leone ◽  
Cecilia Nigro ◽  
Antonella Nicolò ◽  
Immacolata Prevenzano ◽  
Pietro Formisano ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Metabolic Reprogramming ◽  
Therapeutic Approaches ◽  
Hallmarks Of Cancer ◽  
Anti Cancer ◽  
Cellular Apoptosis ◽  
Higher Doses

One of the hallmarks of cancer cells is their metabolic reprogramming, which includes the preference for the use of anaerobic glycolysis to produce energy, even in presence of normal oxygen levels. This phenomenon, known as “Warburg effect”, leads to the increased production of reactive intermediates. Among these Methylglyoxal (MGO), a reactive dicarbonyl known as the major precursor of the advanced glycated end products (AGEs), is attracting great attention. It has been well established that endogenous MGO levels are increased in several types of cancer, however the MGO contribution in tumor progression is still debated. Although an anti-cancer role was initially attributed to MGO due to its cytotoxicity, emerging evidence has highlighted its pro-tumorigenic role in several types of cancer. These apparently conflicting results are explained by the hormetic potential of MGO, in which lower doses of MGO are able to establish an adaptive response in cancer cells while higher doses cause cellular apoptosis. Therefore, the extent of MGO accumulation and the tumor context are crucial to establish MGO contribution to cancer progression. Several therapeutic approaches have been proposed and are currently under investigation to inhibit the pro-tumorigenic action of MGO. In this review, we provide an overview of the early and latest evidence regarding the role of MGO in cancer, in order to define its contribution in tumor progression, and the therapeutic strategies aimed to counteract the tumor growth.

scholarly journals Wnt Signaling in Cancer Metabolism and Immunity

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 904 ◽  
Author(s):  
Sara El-Sahli ◽  
Ying Xie ◽  
Lisheng Wang ◽  
Sheng Liu
Keyword(s):  
Wnt Signaling ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Tumor Initiating Cells ◽  
Tumor Plasticity ◽  
Anti Cancer ◽  
Wnt Ligands ◽  
Canonical Wnt

The Wingless (Wnt)/β-catenin pathway has long been associated with tumorigenesis, tumor plasticity, and tumor-initiating cells called cancer stem cells (CSCs). Wnt signaling has recently been implicated in the metabolic reprogramming of cancer cells. Aberrant Wnt signaling is considered to be a driver of metabolic alterations of glycolysis, glutaminolysis, and lipogenesis, processes essential to the survival of bulk and CSC populations. Over the past decade, the Wnt pathway has also been shown to regulate the tumor microenvironment (TME) and anti-cancer immunity. Wnt ligands released by tumor cells in the TME facilitate the immune evasion of cancer cells and hamper immunotherapy. In this review, we illustrate the role of the canonical Wnt/β-catenin pathway in cancer metabolism and immunity to explore the potential therapeutic approach of targeting Wnt signaling from a metabolic and immunological perspective.

scholarly journals Cancer-specific Therapeutic Potential of Resveratrol: Metabolic Approach against Hallmarks of Cancer

2013 ◽  
Vol 3 (8) ◽  
pp. 332 ◽  
Author(s):  
Dong Hoon Suh ◽  
Mi-Kyung Kim ◽  
Hee Seung Kim ◽  
Hyun Hoon Chung ◽  
Yong Sang Song
Keyword(s):  
Cancer Cells ◽  
Therapeutic Potential ◽  
Metabolic Reprogramming ◽  
Metabolic Demand ◽  
Macromolecular Synthesis ◽  
Invasion And Metastasis ◽  
Hallmarks Of Cancer ◽  
Cancer Hallmarks ◽  
Tissue Invasion ◽  
Anti Cancer

Cancer hallmarks include evading apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion and metastasis. Cancer cells undergo metabolic reprogramming and inevitably take advantage of glycolysis to meet the increased metabolic demand: rapid energy generation and macromolecular synthesis. Resveratrol, a polyphenolic phytoalexin, is known to exhibit pleiotropic anti-cancer effects most of which are linked to metabolic reprogramming in cancer cells. This review summarizes various anti-cancer effects of resveratrol in the context of cancer hallmarks in relation to metabolic reprogramming.

scholarly journals Metabolic Reprogramming of Cancer Cells during Tumor Progression and Metastasis

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 28
Author(s):  
Kenji Ohshima ◽  
Eiichi Morii
Keyword(s):  
Oxidative Stress ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Treatment Strategies ◽  
Primary Site ◽  
Metabolic Reprogramming ◽  
Cancer Growth ◽  
Anchorage Independent Growth ◽  
Underlying Mechanisms

Cancer cells face various metabolic challenges during tumor progression, including growth in the nutrient-altered and oxygen-deficient microenvironment of the primary site, intravasation into vessels where anchorage-independent growth is required, and colonization of distant organs where the environment is distinct from that of the primary site. Thus, cancer cells must reprogram their metabolic state in every step of cancer progression. Metabolic reprogramming is now recognized as a hallmark of cancer cells and supports cancer growth. Elucidating the underlying mechanisms of metabolic reprogramming in cancer cells may help identifying cancer targets and treatment strategies. This review summarizes our current understanding of metabolic reprogramming during cancer progression and metastasis, including cancer cell adaptation to the tumor microenvironment, defense against oxidative stress during anchorage-independent growth in vessels, and metabolic reprogramming during metastasis.

Role of Organ Specific Cancer Stem Cells in Organ Specific Cancer Progression

2020 ◽  
Vol 6 (2) ◽  
pp. 21
Author(s):  
Muhammad Ali ◽  
Fatima Ali ◽  
Nadia Wajid
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Cancer Therapeutics ◽  
Therapeutic Approaches ◽  
Specific Cancer ◽  
Organ Specific

Since the cancer stem cells (CSC) have been identified in 1997 by Bonnet and Dick, more than 100,000 papers have been published on the CSC. Huge research on cancer stem cells helped the scientists to rethink about the cancer therapeutics as classic way of chemotherapy is ineffective because chemotherapy failed to kill these cells, the only reason of cancer relapse. The cancer theory of stem cells is one of the most trending theory in stem cells and cancer biology focusing on the understanding of biology of cancer cells for an enhanced and improved therapeutic approaches should be applied to cure the cancer. This mini-review is a short overview on the role of organ specific cancer stem cells in the organ specific cancer progression.

Cancer cells, adipocytes and matrix metalloproteinase 11: a vicious tumor progression cycle

2008 ◽  
Vol 389 (8) ◽  
Author(s):  
Elena Roza Motrescu ◽  
Marie-Christine Rio
Keyword(s):  
Matrix Metalloproteinase ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Adipocyte Differentiation ◽  
Mature Adipocyte ◽  
Surrounding Environment ◽  
Cancer Cell Survival ◽  
Obesity And Cancer

Abstract This brief review focuses on the emerging role of matrix metalloproteinase 11 (MMP-11) in cancer progression. It has recently been shown that MMP-11 is induced in adipose tissue by cancer cells as they invade their surrounding environment. MMP-11 negatively regulates adipogenesis by reducing pre-adipocyte differentiation and reversing mature adipocyte differentiation. Adipocyte dedifferentiation in turn leads to the accumulation of non-malignant peritumoral fibroblast-like cells, which favor cancer cell survival and tumor progression. This MMP-11-mediated bi-directional cross-talk between invading cancer cells and adjacent adipocytes/pre-adipocytes highlights the central role that MMP-11 plays during tumor desmoplasia and represents a molecular link between obesity and cancer.

scholarly journals Exosome-mediated metabolic reprogramming: the emerging role in tumor microenvironment remodeling and its influence on cancer progression

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Enli Yang ◽  
Xuan Wang ◽  
Zhiyuan Gong ◽  
Miao Yu ◽  
Haiwei Wu ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Potential Role ◽  
Tumor Development ◽  
Underlying Mechanism ◽  
Metabolic Reprogramming ◽  
Diagnosis And Prognosis ◽  
Energy Demands

Abstract Metabolic reprogramming is reported to be one of the hallmarks of cancer, which is an adaptive mechanism by which fast-growing cancer cells adapt to their increasing energy demands. Recently, extracellular vesicles (EVs) known as exosomes have been recognized as crucial signaling mediators in regulating the tumor microenvironment (TME). Meanwhile, the TME is a highly heterogeneous ecosystem incorporating cancer cells, fibroblasts, adipocytes, endothelial cells, mesenchymal stem cells, and extracellular matrix. Accumulated evidence indicates that exosomes may transfer biologically functional molecules to the recipient cells, which facilitate cancer progression, angiogenesis, metastasis, drug resistance, and immunosuppression by reprogramming the metabolism of cancer cells and their surrounding stromal cells. In this review, we present the role of exosomes in the TME and the underlying mechanism of how exosomes exacerbate tumor development through metabolic reprogramming. In addition, we will also discuss the potential role of exosomes targeting metabolic process as biomarkers for tumor diagnosis and prognosis, and exosomes-mediated metabolic reprogramming as potential targets for cancer therapy. Furthermore, a better understanding of the link between exosomes and metabolic reprogramming, and their impact on cancer progression, would provide novel insights for cancer prevention and treatment in the future.

scholarly journals Metabolic Escape Routes of Cancer Stem Cells and Therapeutic Opportunities

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1436 ◽  
Author(s):  
Alice Turdo ◽  
Gaetana Porcelli ◽  
Caterina D’Accardo ◽  
Simone Di Franco ◽  
Francesco Verona ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Therapeutic Approaches ◽  
Current Therapies ◽  
Oxidative Phenotype

Although improvement in early diagnosis and treatment ameliorated life expectancy of cancer patients, metastatic disease still lacks effective therapeutic approaches. Resistance to anticancer therapies stems from the refractoriness of a subpopulation of cancer cells—termed cancer stem cells (CSCs)—which is endowed with tumor initiation and metastasis formation potential. CSCs are heterogeneous and diverge by phenotypic, functional and metabolic perspectives. Intrinsic as well as extrinsic stimuli dictated by the tumor microenvironment (TME)have critical roles in determining cell metabolic reprogramming from glycolytic toward an oxidative phenotype and vice versa, allowing cancer cells to thrive in adverse milieus. Crosstalk between cancer cells and the surrounding microenvironment occurs through the interchange of metabolites, miRNAs and exosomes that drive cancer cells metabolic adaptation. Herein, we identify the metabolic nodes of CSCs and discuss the latest advances in targeting metabolic demands of both CSCs and stromal cells with the scope of improving current therapies and preventing cancer progression.

scholarly journals mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression

2018 ◽  
Vol 19 (10) ◽  
pp. 3267 ◽  
Author(s):  
Mio Harachi ◽  
Kenta Masui ◽  
Yukinori Okamura ◽  
Ryota Tsukui ◽  
Paul Mischel ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Cancer Cell Survival

Recent advancement in the field of molecular cancer research has clearly revealed that abnormality of oncogenes or tumor suppressor genes causes tumor progression thorough the promotion of intracellular metabolism. Metabolic reprogramming is one of the strategies for cancer cells to ensure their survival by enabling cancer cells to obtain the macromolecular precursors and energy needed for the rapid growth. However, an orchestration of appropriate metabolic reactions for the cancer cell survival requires the precise mechanism to sense and harness the nutrient in the microenvironment. Mammalian/mechanistic target of rapamycin (mTOR) complexes are known downstream effectors of many cancer-causing mutations, which are thought to regulate cancer cell survival and growth. Recent studies demonstrate the intriguing role of mTOR to achieve the feat through metabolic reprogramming in cancer. Importantly, not only mTORC1, a well-known regulator of metabolism both in normal and cancer cell, but mTORC2, an essential partner of mTORC1 downstream of growth factor receptor signaling, controls cooperatively specific metabolism, which nominates them as an essential regulator of cancer metabolism as well as a promising candidate to garner and convey the nutrient information from the surrounding environment. In this article, we depict the recent findings on the role of mTOR complexes in cancer as a master regulator of cancer metabolism and a potential sensor of nutrients, especially focusing on glucose and amino acid sensing in cancer. Novel and detailed molecular mechanisms that amino acids activate mTOR complexes signaling have been identified. We would also like to mention the intricate crosstalk between glucose and amino acid metabolism that ensures the survival of cancer cells, but at the same time it could be exploitable for the novel intervention to target the metabolic vulnerabilities of cancer cells.

scholarly journals Metabolic Reprogramming in Thyroid Cancer: Role of the Epithelial-Mesenchymal Transition

Endocrines ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 427-438
Author(s):  
Monica Fedele ◽  
Sabrina Battista ◽  
Laura Cerchia
Keyword(s):  
Thyroid Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Anaplastic Thyroid Carcinoma ◽  
Metabolic Changes ◽  
Metabolic Reprogramming ◽  
Mesenchymal Transition

Thyroid cancer (TC) represents the most common endocrine malignancy, with an increasing incidence all over the world. Papillary TC (PTC), a differentiated TC subtype, is the most common and, even though it has an excellent prognosis following radioiodine (RAI) ablation, it shows an aggressive behavior in 20–30% of cases, becoming RAI-resistant and/or metastatic. On the other side, anaplastic thyroid carcinoma (ATC), the most undifferentiated TC, is a rare but devastating disease, indicating that progression of differentiated to undifferentiated forms of TC could be responsible for RAI-resistance and increased mortality. The epithelial-to-mesenchymal transition (EMT) plays a pivotal role in both tumor progression and resistance to therapy. Moreover, during tumor progression, cancer cells modify their metabolism to meet changed requirements for cellular proliferation. Through these metabolic changes, cancer cells may adopt cancer stem cell-like properties and express an EMT phenotype. EMT, in turn, can induce metabolic changes to which cancer cells become addicted. Here we review metabolic reprogramming in TC highlighting the role of EMT with the aim to explore a potential field to find out new therapeutic strategies for advanced-stage PTC. Accordingly, we discuss the identification of the metabolic enzymes and metabolites, critical to TC progression, which can be employed either as predicting biomarkers of tumor response to RAI therapy or possible targets in precision medicine.

scholarly journals The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin

2021 ◽  
Vol 22 (17) ◽  
pp. 9546
Author(s):  
Diego Assis Gonçalves ◽  
Miriam Galvonas Jasiulionis ◽  
Fabiana Henriques Machado de Melo
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Control Cell ◽  
Metabolic Reprogramming ◽  
Main Function ◽  
Oncogenic Signaling ◽  
Oxide Synthase

Cancer development is associated with abnormal proliferation, genetic instability, cell death resistance, metabolic reprogramming, immunity evasion, and metastasis. These alterations are triggered by genetic and epigenetic alterations in genes that control cell homeostasis. Increased reactive oxygen and nitrogen species (ROS, RNS) induced by different enzymes and reactions with distinct molecules contribute to malignant transformation and tumor progression by modifying DNA, proteins, and lipids, altering their activities. Nitric oxide synthase plays a central role in oncogenic signaling modulation and redox landscape. Overexpression of the three NOS isoforms has been found in innumerous types of cancer contributing to tumor growth and development. Although the main function of NOS is the production of nitric oxide (NO), it can be a source of ROS in some pathological conditions. Decreased tetrahydrobiopterin (BH4) cofactor availability is involved in NOS dysfunction, leading to ROS production and reduced levels of NO. The regulation of NOSs by BH4 in cancer is controversial since BH4 has been reported as a pro-tumoral or an antitumoral molecule. Therefore, in this review, the role of BH4 in the control of NOS activity and its involvement in the capabilities acquired along tumor progression of different cancers was described.

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