scholarly journals WNT Signaling: an Emerging Mediator of Cancer Cell Metabolism?

2014 ◽  
Vol 35 (1) ◽  
pp. 2-10 ◽  
Author(s):  
Victoria Sherwood
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Cancer Cell ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Critical Role ◽  
Oncogenic Signaling ◽  
Cancer Cell Metabolism ◽  
Oncogenic Signaling Pathways

WNT signaling was discovered in tumor models and has been recognized as a regulator of cancer development and progression for over 3 decades. Recent work has highlighted a critical role for WNT signaling in the metabolic homeostasis of mammals, where its misregulation has been heavily implicated in diabetes. While the majority of WNT metabolism research has focused on nontransformed tissues, the role of WNT in cancer metabolism remains underinvestigated. Cancer is also a metabolic disease where oncogenic signaling pathways regulate energy production and macromolecular synthesis to fuel rapidly proliferating tumors. This review highlights the emerging evidence for WNT signaling in the reprogramming of cancer cell metabolism and examines the role of these signaling pathways as mediators of tumor bioenergetics.

scholarly journals Oncolytic Virotherapy: The Cancer Cell Side

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 939
Author(s):  
Marcelo Ehrlich ◽  
Eran Bacharach
Keyword(s):  
Viral Replication ◽  
Cancer Cell ◽  
Cell Metabolism ◽  
Tumor Development ◽  
Oncolytic Viruses ◽  
Oncogenic Signaling ◽  
Functional Connection ◽  
Immunity Genes ◽  
Cancer Cell Metabolism ◽  
Editing Process

Cell autonomous immunity genes mediate the multiple stages of anti-viral defenses, including recognition of invading pathogens, inhibition of viral replication, reprogramming of cellular metabolism, programmed-cell-death, paracrine induction of antiviral state, and activation of immunostimulatory inflammation. In tumor development and/or immunotherapy settings, selective pressure applied by the immune system results in tumor immunoediting, a reduction in the immunostimulatory potential of the cancer cell. This editing process comprises the reduced expression and/or function of cell autonomous immunity genes, allowing for immune-evasion of the tumor while concomitantly attenuating anti-viral defenses. Combined with the oncogene-enhanced anabolic nature of cancer-cell metabolism, this attenuation of antiviral defenses contributes to viral replication and to the selectivity of oncolytic viruses (OVs) towards malignant cells. Here, we review the manners by which oncogene-mediated transformation and tumor immunoediting combine to alter the intracellular milieu of tumor cells, for the benefit of OV replication. We also explore the functional connection between oncogenic signaling and epigenetic silencing, and the way by which restriction of such silencing results in immune activation. Together, the picture that emerges is one in which OVs and epigenetic modifiers are part of a growing therapeutic toolbox that employs activation of anti-tumor immunity for cancer therapy.

scholarly journals Peroxisome Metabolism in Cancer

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1692 ◽  
Author(s):  
Jung-Ae Kim
Keyword(s):  
Metabolic Pathways ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Critical Role ◽  
Acid Oxidation ◽  
Metabolic Dysregulation ◽  
Human Disorders ◽  
Peroxisomal Function ◽  
Target Cancer

Peroxisomes are metabolic organelles involved in lipid metabolism and cellular redoxbalance. Peroxisomal function is central to fatty acid oxidation, ether phospholipid synthesis, bile acidsynthesis, and reactive oxygen species homeostasis. Human disorders caused by genetic mutations inperoxisome genes have led to extensive studies on peroxisome biology. Peroxisomal defects are linkedto metabolic dysregulation in diverse human diseases, such as neurodegeneration and age-relateddisorders, revealing the significance of peroxisome metabolism in human health. Cancer is a diseasewith metabolic aberrations. Despite the critical role of peroxisomes in cell metabolism, the functionaleects of peroxisomes in cancer are not as well recognized as those of other metabolic organelles,such as mitochondria. In addition, the significance of peroxisomes in cancer is less appreciated thanit is in degenerative diseases. In this review, I summarize the metabolic pathways in peroxisomesand the dysregulation of peroxisome metabolism in cancer. In addition, I discuss the potential ofinactivating peroxisomes to target cancer metabolism, which may pave the way for more eectivecancer treatment.

scholarly journals Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine

2017 ◽  
Vol 36 (10) ◽  
pp. 1302-1315 ◽  
Author(s):  
Ji Zhang ◽  
Natalya N Pavlova ◽  
Craig B Thompson
Keyword(s):  
Amino Acid ◽  
Cancer Cell ◽  
Essential Role ◽  
Cell Metabolism ◽  
Nonessential Amino Acid ◽  
Cancer Cell Metabolism

scholarly journals Targeting PAK1

2017 ◽  
Vol 45 (1) ◽  
pp. 79-88 ◽  
Author(s):  
Galina Semenova ◽  
Jonathan Chernoff
Keyword(s):  
Signaling Pathways ◽  
Peptide Inhibitors ◽  
Oncogenic Signaling ◽  
Allosteric Inhibitors ◽  
Small Molecule Inhibition ◽  
Pharmacokinetic Properties ◽  
Competitive Inhibitors ◽  
P21 Activated Kinase ◽  
Oncogenic Signaling Pathways

p21-Activated kinase 1 (PAK1) has attracted much attention as a potential therapeutic target due to its central role in many oncogenic signaling pathways, its frequent dysregulation in cancers and neurological disorders, and its tractability as a target for small-molecule inhibition. To date, several PAK1-targeting compounds have been developed as preclinical agents, including one that has been evaluated in a clinical trial. A series of ATP-competitive inhibitors, allosteric inhibitors and peptide inhibitors with distinct biochemical and pharmacokinetic properties represent useful laboratory tools for studies on the role of PAK1 in biology and in disease contexts, and could lead to promising therapeutic agents. Given the central role of PAK1 in vital signaling pathways, future clinical development of PAK1 inhibitors will require careful investigation of their safety and efficacy.

scholarly journals Regulation of Canonical Oncogenic Signaling Pathways in Cancer via DNA Methylation

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3199
Author(s):  
Jennifer Lu ◽  
Premila Wilfred ◽  
Darren Korbie ◽  
Matt Trau
Keyword(s):  
Dna Methylation ◽  
Signaling Pathways ◽  
Biomarker Discovery ◽  
Oncogenic Signaling ◽  
Tissue Samples ◽  
Epigenetic Biomarkers ◽  
Differentially Methylated Genes ◽  
Oncogenic Signaling Pathways ◽  
Integration Analysis

Disruption of signaling pathways that plays a role in the normal development and cellular homeostasis may lead to the dysregulation of cellular signaling and bring about the onset of different diseases, including cancer. In addition to genetic aberrations, DNA methylation also acts as an epigenetic modifier to drive the onset and progression of cancer by mediating the reversible transcription of related genes. Although the role of DNA methylation as an alternative driver of carcinogenesis has been well-established, the global effects of DNA methylation on oncogenic signaling pathways and the presentation of cancer is only emerging. In this article, we introduced a differential methylation parsing pipeline (MethylMine) which mined for epigenetic biomarkers based on feature selection. This pipeline was used to mine for biomarkers, which presented a substantial difference in methylation between the tumor and the matching normal tissue samples. Combined with the Data Integration Analysis for Biomarker discovery (DIABLO) framework for machine learning and multi-omic analysis, we revisited the TCGA DNA methylation and RNA-Seq datasets for breast, colorectal, lung, and prostate cancer, and identified differentially methylated genes within the NRF2-KEAP1/PI3K oncogenic pathway, which regulates the expression of cytoprotective genes, that serve as potential therapeutic targets to treat different cancers.

scholarly journals GM2-GM3 gangliosides ratio is dependent on GRP94 through down-regulation of GM2-AP cofactor in brain metastasis cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Carmen Bedia ◽  
Miriam Badia ◽  
Laia Muixí ◽  
Thierry Levade ◽  
Romà Tauler ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Critical Role ◽  
Surface Dynamics ◽  
Oncogenic Signaling ◽  
Cell Behaviour ◽  
Lipid Species ◽  
Lysosomal Accumulation ◽  
Oncogenic Signaling Pathways ◽  
Hydrolysis Of

Abstract GRP94 is an ATP-dependent chaperone able to regulate pro-oncogenic signaling pathways. Previous studies have shown a critical role of GRP94 in brain metastasis (BrM) pathogenesis and progression. In this work, an untargeted lipidomic analysis revealed that some lipid species were altered in GRP94-deficient cells, specially GM2 and GM3 gangliosides. The catalytic pathway of GM2 is affected by the low enzymatic activity of β-Hexosaminidase (HexA), responsible for the hydrolysis of GM2 to GM3. Moreover, a deficiency of the GM2-activator protein (GM2-AP), the cofactor of HexA, is observed without alteration of gene expression, indicating a post-transcriptional alteration of GM2-AP in the GRP94-ablated cells. One plausible explanation of these observations is that GM2-AP is a client of GRP94, resulting in defective GM2 catabolic processing and lysosomal accumulation of GM2 in GRP94-ablated cells. Overall, given the role of gangliosides in cell surface dynamics and signaling, their imbalance might be linked to modifications of cell behaviour acquired in BrM progression. This work indicates that GM2-AP could be an important factor in ganglioside balance maintenance. These findings highlight the relevance of GM3 and GM2 gangliosides in BrM and reveal GM2-AP as a promising diagnosis and therapeutic target in BrM research.

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