&lt;p&gt;Phosphoglycerate Mutase 1: Its Glycolytic and Non-Glycolytic Roles in Tumor Malignant Behaviors and Potential Therapeutic Significance&lt;/p&gt;

Tian

et al. 2021

Preprint

Introduction The glycolytic enzyme, α-Enolase (ENO1), catalyzes the production of phosphoenolpyruvate from 2-phosphoglycerate, which enhances glycolysis, and thus contributes to tumor progression. In the present study, we aimed to determine ENO1’s role in malignant melanoma (MM) and the potential underlying mechanism. Methods Western blotting was used to assess the levels of ENO1, c-Myc, β-catenin, MMP-9, PGAM1, and MMP-13 in MM-derived cell lines or tumor tissues from patients with MM. Plasmids pCMV-SPORT6-ENO1 and pET-28a-ENO1siRNA plasmids were used to overexpress and knockdown ENO1 in MM cells, respectively. To determine the function of ENO1 in the malignant behavior of MM cells, we performed wound healing, Cell counting kit 8, Transwell chamber, and flow cytometry analyses. Pyruvate determination and lactic acid kits were used to evaluate the production of pyruvate and lactic acid in tumor cells. Results The protein levels of ENO1 and PGAM1 in MM tissue were significantly higher than that in mole tissue. In MM cells, ENO1 overexpression inhibited apoptosis; promoted invasion, migration, and proliferation; increased pyruvate and lactate production; and increased in β-catenin, MMP-9, MMP-13, and c-Myc levels. The opposite effects were observed in MM cells silenced for ENO1. Conclusion These results indicated that ENO1 is involved in MM progression by enhancing invasion and proliferation, while inhibiting apoptosis. In addition, ENO1 might have an important function in tumor cell glycolysis. Therefore, ENO1 represents a potential therapeutic target to treat MM.

Section: Discussionmentioning

confidence: 99%

ENO1 Inhibits Apoptosis and Promotes Cell Invasion and Proliferation in Malignant Melanoma

Tian

et al. 2021

Preprint

“…In addition, phosphoglycerate mutase 1 (PGAM1) catalyzes the reversible conversion of 3-phosphoglycerate and 2-phosphoglycerate during glycolysis. PGAM1 is overexpressed in various cancer tissues and plays an essential role in cancer progression and metastasis [ 47 ]. Moreover, enolase is a key glycolytic enzyme that converts 2-bisphosphate glycerate into phosphoenolpyruvate.…”

Section: Glucose Metabolism (Glycolysis) In Tumors and The Warburgmentioning

confidence: 99%

Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism

Brockmueller

Sameri

Líšková

et al. 2021

Cancers

Tumor cells develop several metabolic reprogramming strategies, such as increased glucose uptake and utilization via aerobic glycolysis and fermentation of glucose to lactate; these lead to a low pH environment in which the cancer cells thrive and evade apoptosis. These characteristics of tumor cells are known as the Warburg effect. Adaptive metabolic alterations in cancer cells can be attributed to mutations in key metabolic enzymes and transcription factors. The features of the Warburg phenotype may serve as promising markers for the early detection and treatment of tumors. Besides, the glycolytic process of tumors is reversible and could represent a therapeutic target. So-called mono-target therapies are often unsafe and ineffective, and have a high prevalence of recurrence. Their success is hindered by the ability of tumor cells to simultaneously develop multiple chemoresistance pathways. Therefore, agents that modify several cellular targets, such as energy restriction to target tumor cells specifically, have therapeutic potential. Resveratrol, a natural active polyphenol found in grapes and red wine and used in many traditional medicines, is known for its ability to target multiple components of signaling pathways in tumors, leading to the suppression of cell proliferation, activation of apoptosis, and regression in tumor growth. Here, we describe current knowledge on the various mechanisms by which resveratrol modulates glucose metabolism, its potential as an imitator of caloric restriction, and its therapeutic capacity in tumors.

“…Moreover, in malignant tumor cells several glycolytic enzymes can be upregulated. For example, the PGAM1 [ 49 ], PKM2 [ 50 ], HK2 [ 51 ], and GAPDH [ 52 ] are often upregulated in tumor cells, PFK results increased in various breast tumors [ 53 ], enolase in pancreatic ductal adenocarcinoma [ 54 ], and aldolase in the lung’s squamous cell carcinoma [ 55 ]. In summary, all these enzymes may be potential targets for the treatment of malignant tumors.…”

Section: Glucose Metabolism Alteration In Cancer Cellsmentioning

confidence: 99%

Targeting the Interplay between Cancer Metabolic Reprogramming and Cell Death Pathways as a Viable Therapeutic Path

et al. 2021

In cancer cells, metabolic adaptations are often observed in terms of nutrient absorption, biosynthesis of macromolecules, and production of energy necessary to meet the needs of the tumor cell such as uncontrolled proliferation, dissemination, and acquisition of resistance to death processes induced by both unfavorable environmental conditions and therapeutic drugs. Many oncogenes and tumor suppressor genes have a significant effect on cellular metabolism, as there is a close relationship between the pathways activated by these genes and the various metabolic options. The metabolic adaptations observed in cancer cells not only promote their proliferation and invasion, but also their survival by inducing intrinsic and acquired resistance to various anticancer agents and to various forms of cell death, such as apoptosis, necroptosis, autophagy, and ferroptosis. In this review we analyze the main metabolic differences between cancer and non-cancer cells and how these can affect the various cell death pathways, effectively determining the susceptibility of cancer cells to therapy-induced death. Targeting the metabolic peculiarities of cancer could represent in the near future an innovative therapeutic strategy for the treatment of those tumors whose metabolic characteristics are known.