scholarly journals Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

2021 ◽  
Vol 22 (12) ◽  
pp. 6434
Author(s):  
Aldona Kasprzak
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Glucose Metabolism ◽  
Warburg Effect ◽  
Mapk Signaling ◽  
Colorectal Carcinogenesis ◽  
Insulin Like Growth Factor ◽  
Aberrant Expression ◽  
The Warburg Effect

Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-β1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.

scholarly journals Genetic Mutations and Non-Coding RNA-Based Epigenetic Alterations Mediating the Warburg Effect in Colorectal Carcinogenesis

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 847
Author(s):  
Batoul Abi Zamer ◽  
Wafaa Abumustafa ◽  
Mawieh Hamad ◽  
Azzam A. Maghazachi ◽  
Jibran Sualeh Muhammad
Keyword(s):  
Colorectal Cancer ◽  
Glucose Metabolism ◽  
Warburg Effect ◽  
Colorectal Carcinogenesis ◽  
Genetic Mutations ◽  
Epigenetic Alterations ◽  
Therapeutic Approaches ◽  
Non Coding Rna ◽  
Gradual Process ◽  
The Warburg Effect

Colorectal cancer (CRC) development is a gradual process defined by the accumulation of numerous genetic mutations and epigenetic alterations leading to the adenoma-carcinoma sequence. Despite significant advances in the diagnosis and treatment of CRC, it continues to be a leading cause of cancer-related deaths worldwide. Even in the presence of oxygen, CRC cells bypass oxidative phosphorylation to produce metabolites that enable them to proliferate and survive—a phenomenon known as the “Warburg effect”. Understanding the complex glucose metabolism in CRC cells may support the development of new diagnostic and therapeutic approaches. Here we discuss the most recent findings on genetic mutations and epigenetic modulations that may positively or negatively regulate the Warburg effect in CRC cells. We focus on the non-coding RNA (ncRNA)-based epigenetics, and we present a perspective on the therapeutic relevance of critical molecules and ncRNAs mediating the Warburg effect in CRC cells. All the relevant studies were identified and assessed according to the genes and enzymes mediating the Warburg effect. The findings summarized in this review should provide a better understanding of the relevance of genetic mutations and the ncRNA-based epigenetic alterations to CRC pathogenesis to help overcome chemoresistance.

scholarly journals Evolved resistance to GAPDH inhibition results in loss of the Warburg Effect but retains a different state of glycolysis

2019 ◽  
Author(s):  
Maria V. Liberti ◽  
Annamarie E. Allen ◽  
Vijyendra Ramesh ◽  
Ziwei Dai ◽  
Katherine R. Singleton ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Warburg Effect ◽  
Acid Metabolism ◽  
Aerobic Glycolysis ◽  
Specific Inhibitor ◽  
Central Carbon Metabolism ◽  
Glycolytic Enzyme ◽  
Altered State ◽  
The Warburg Effect

SUMMARYAerobic glycolysis or the Warburg Effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although ubiquitous, the biological role of the WE remains controversial and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, we evolved resistance to koningic acid (KA), a natural product shown to be a specific inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme during the WE. We find that KA-resistant cells lose the WE but conduct glycolysis and surprisingly remain dependent on glucose and central carbon metabolism. Consequentially this altered state of glycolysis leads to differential metabolic activity and requirements including emergent activities in and dependencies on fatty acid metabolism. Together, these findings reveal that, contrary to some recent reports, aerobic glycolysis is a functionally distinct entity from conventional glucose metabolism and leads to distinct metabolic requirements and biological functions.

scholarly journals Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect

2011 ◽  
Vol 108 (39) ◽  
pp. 16259-16264 ◽  
Author(s):  
C. Zhang ◽  
M. Lin ◽  
R. Wu ◽  
X. Wang ◽  
B. Yang ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Warburg Effect ◽  
Target Gene ◽  
P53 Target Gene ◽  
The Warburg Effect

The role of the insulin-like growth factor system in colorectal cancer: review of current knowledge

2005 ◽  
Vol 20 (3) ◽  
pp. 203-220 ◽  
Author(s):  
Rajaraman Durai ◽  
Wenxuan Yang ◽  
Sharmila Gupta ◽  
Alexander M. Seifalian ◽  
Marc C. Winslet
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Current Knowledge ◽  
Insulin Like Growth Factor ◽  
Cancer Review ◽  
Factor System

scholarly journals Influence of SNF1 complex on growth, glucose metabolism and mitochondrial respiration ofSaccharomyces cerevisiae

2018 ◽  
Author(s):  
Cecilia Martinez-Ortiz ◽  
Andres Carrillo-Garmendia ◽  
Blanca Flor Correa-Romero ◽  
Melina Canizal-García ◽  
Juan Carlos González-Hernández ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Mitochondrial Respiration ◽  
Warburg Effect ◽  
Gene Deletion ◽  
Glycolytic Flux ◽  
Crabtree Effect ◽  
Main Pathway ◽  
Molecular Etiology ◽  
The Warburg Effect

AbstractThe switch of mitochondrial respiration to fermentation as the main pathway to produce ATP through the increase of glycolytic flux is known as the Crabtree effect. The elucidation of the molecular mechanism of the Crabtree effect may have important applications in ethanol production and lay the groundwork for the Warburg effect, which is essential in the molecular etiology of cancer. A key piece in this mechanism could be Snf1p, which is a protein that participates in the nutritional response that includes glucose metabolism. Thus, this work aimed to recognize the role of the SNF1 complex on the glycolytic flux and mitochondrial respiration, to gain insights about its relationship with the Crabtree effect. Herein, we found that inSaccharomyces cerevisiaecells grown at 1% glucose, mutation ofSNF1gene decreased glycolytic flux, increased NAD(P)H, enhancedHXK2gene transcription, and decreased mitochondrial respiration. Meanwhile, the same mutation increased the mitochondrial respiration of cells grown at 10% glucose. Moreover,SNF4gene deletion increased respiration and growth at 1% of glucose. In the case of theGAL83gene, we did not detect any change in mitochondrial respiration or growth. Altogether, these findings indicate thatSNF1is vital to switch from mitochondrial respiration to fermentation.

scholarly journals Circular RNAs: A New Piece in the Colorectal Cancer Puzzle

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2464 ◽  
Author(s):  
Pinelopi I. Artemaki ◽  
Andreas Scorilas ◽  
Christos K. Kontos
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinogenesis ◽  
Circular Rnas ◽  
Aberrant Splicing ◽  
Aberrant Expression ◽  
Transcription Regulators ◽  
Molecular Base ◽  
By Products ◽  
Microrna Sponges

Colorectal cancer (CRC) is the third most fatal type of malignancy, worldwide. Despite the advances accomplished in the elucidation of its molecular base and the existing CRC biomarkers introduced in the clinical practice, additional research is required. Circular RNAs (circRNAs) constitute a new RNA type, formed by back-splicing of primary transcripts. They have been discovered during the 1970s but were characterized as by-products of aberrant splicing. However, the modern high-throughput approaches uncovered their widespread expression; therefore, several questions were raised regarding their potential biological roles. During the last years, great progress has been achieved in the elucidation of their functions: circRNAs can act as microRNA sponges, transcription regulators, and interfere with splicing, as well. Furthermore, they are heavily involved in various human pathological states, including cancer, and could serve as diagnostic and prognostic biomarkers in several diseases. Particularly in CRC, aberrant expression of circRNAs has been observed. More specifically, these molecules either inhibit or promote colorectal carcinogenesis by regulating different molecules and signaling pathways. The present review discusses the characteristics and functions of circRNA, prior to analyzing the multifaceted role of these molecules in CRC and their potential value as biomarkers and therapeutic targets.

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