Signalling Pathways Implicated in Obesity Associated Cancers

Intensive research over recent years has provided irrefutable evidence of links between obesity and the risk of an increasing number of human cancers. The predicted economic burden is causing significant concern. This has prompted investigation of the underlying mechanisms with a focus on deregulated metabolic pathways. A number of metabolic processes and associated signalling pathways are associated with the development of obesity. These include a number of interlinking pathways regulating endocrine, redox, inflammation, immunity and lipogenic processes. The identification of deregulated metabolic pathways in obesity with promotion of carcinogenesis has targeted research on the signalling molecules involved. Consequently this mini review is focused on aberrant signalling of deregulated pathways provoked by diets that lead to obesity and their role in carcinogenesis. Knowledge of the signalling molecules involved will assist in directing and establishing dietary manipulation strategies to restore metabolic health in obese individuals. Importantly the identified diversity of signalling pathways linked to obesity related cancers will permit design of more effective combinatorial and multi-targeted cancer therapies in the future.

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Mechanisms and Insights for the Development of Heart Failure Associated with Cancer Therapy

Children ◽

10.3390/children8090829 ◽

2021 ◽

Vol 8 (9) ◽

pp. 829

Author(s):

Claire Fraley ◽

Sarah A. Milgrom ◽

Lavanya Kondapalli ◽

Matthew R. G. Taylor ◽

Luisa Mestroni ◽

...

Keyword(s):

Stem Cell ◽

Induced Pluripotent Stem Cell ◽

Childhood Cancer Survivors ◽

Cardiovascular Complications ◽

Cancer Therapies ◽

Hematopoietic Stem ◽

Targeted Cancer Therapies ◽

Underlying Mechanisms ◽

Induced Pluripotent

Cardiotoxicity is a well-recognized late effect among childhood cancer survivors. With various pediatric cancers becoming increasingly curable, it is imperative to understand the disease burdens that survivors may face in the future. In order to prevent or mitigate cardiovascular complications, we must first understand the mechanistic underpinnings. This review will examine the underlying mechanisms of cardiotoxicity that arise from traditional antineoplastic chemotherapies, radiation therapy, hematopoietic stem cell transplantation, as well as newer cellular therapies and targeted cancer therapies. We will then propose areas for prevention, primarily drawing from the anthracycline-induced cardiotoxicity literature. Finally, we will explore the role of human induced pluripotent stem cell cardiomyocytes and genetics in advancing the field of cardio-oncology.

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Ties that bind: the integration of plastid signalling pathways in plant cell metabolism

Essays in Biochemistry ◽

10.1042/ebc20170011 ◽

2018 ◽

Vol 62 (1) ◽

pp. 95-107 ◽

Cited By ~ 17

Author(s):

Jacob O. Brunkard ◽

Tessa M. Burch-Smith

Keyword(s):

Metabolic Pathways ◽

Potential Role ◽

Cell Metabolism ◽

Signalling Pathways ◽

Primary Metabolism ◽

Tetrapyrrole Biosynthesis ◽

Life And Death ◽

Signalling Molecules ◽

Signal Transduction Networks

Plastids are critical organelles in plant cells that perform diverse functions and are central to many metabolic pathways. Beyond their major roles in primary metabolism, of which their role in photosynthesis is perhaps best known, plastids contribute to the biosynthesis of phytohormones and other secondary metabolites, store critical biomolecules, and sense a range of environmental stresses. Accordingly, plastid-derived signals coordinate a host of physiological and developmental processes, often by emitting signalling molecules that regulate the expression of nuclear genes. Several excellent recent reviews have provided broad perspectives on plastid signalling pathways. In this review, we will highlight recent advances in our understanding of chloroplast signalling pathways. Our discussion focuses on new discoveries illuminating how chloroplasts determine life and death decisions in cells and on studies elucidating tetrapyrrole biosynthesis signal transduction networks. We will also examine the role of a plastid RNA helicase, ISE2, in chloroplast signalling, and scrutinize intriguing results investigating the potential role of stromules in conducting signals from the chloroplast to other cellular locations.

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91 Retinopathy Secondary to Targeted Cancer Therapies

The Retina Illustrated ◽

10.1055/b-0040-174276 ◽

2020 ◽

Keyword(s):

Cancer Therapies ◽

Targeted Cancer Therapies

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Senolytics for Cancer Therapy: Is All that Glitters Really Gold?

Cancers ◽

10.3390/cancers13040723 ◽

2021 ◽

Vol 13 (4) ◽

pp. 723

Author(s):

Valerie J. Carpenter ◽

Tareq Saleh ◽

David A. Gewirtz

Keyword(s):

Cancer Therapy ◽

Tumor Cell ◽

Cancer Therapies ◽

Cell Models ◽

Future Directions ◽

Targeted Cancer Therapies

Senolytics represent a group of mechanistically diverse drugs that can eliminate senescent cells, both in tumors and in several aging-related pathologies. Consequently, senolytic use has been proposed as a potential adjuvant approach to improve the response to senescence-inducing conventional and targeted cancer therapies. Despite the unequivocal promise of senolytics, issues of universality, selectivity, resistance, and toxicity remain to be further clarified. In this review, we attempt to summarize and analyze the current preclinical literature involving the use of senolytics in senescent tumor cell models, and to propose tenable solutions and future directions to improve the understanding and use of this novel class of drugs.

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Metabolome and proteome analyses reveal transcriptional misregulation in glycolysis of engineered E. coli

Nature Communications ◽

10.1038/s41467-021-25142-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Chun-Ying Wang ◽

Martin Lempp ◽

Niklas Farke ◽

Stefano Donati ◽

Timo Glatter ◽

...

Keyword(s):

Transcription Factor ◽

Binding Site ◽

Metabolic Pathways ◽

Glycerol Production ◽

Inducible Promoters ◽

E Coli ◽

Inhibition Of Glycolysis ◽

Underlying Mechanisms ◽

Rate Limiting ◽

Engineered Bacteria

AbstractSynthetic metabolic pathways are a burden for engineered bacteria, but the underlying mechanisms often remain elusive. Here we show that the misregulated activity of the transcription factor Cra is responsible for the growth burden of glycerol overproducing E. coli. Glycerol production decreases the concentration of fructose-1,6-bisphoshate (FBP), which then activates Cra resulting in the downregulation of glycolytic enzymes and upregulation of gluconeogenesis enzymes. Because cells grow on glucose, the improper activation of gluconeogenesis and the concomitant inhibition of glycolysis likely impairs growth at higher induction of the glycerol pathway. We solve this misregulation by engineering a Cra-binding site in the promoter controlling the expression of the rate limiting enzyme of the glycerol pathway to maintain FBP levels sufficiently high. We show the broad applicability of this approach by engineering Cra-dependent regulation into a set of constitutive and inducible promoters, and use one of them to overproduce carotenoids in E. coli.

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