The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2652 - 2652

Published: Jan. 31, 2023

Hepatocellular carcinoma (HCC) is one of the leading causes cancer-related deaths in world. Metabolic reprogramming considered a new hallmark cancer, but it remains unclearly described HCC. The dysregulation PI3K/AKT/mTOR signaling pathway common HCC and is, therefore, topic further research concern developing novel target for liver cancer therapy. In this review, we illustrate mechanisms by which network accountable regulating cellular metabolism, including glucose lipid amino acid pyrimidine oxidative summarize ongoing clinical trials based on inhibition

Language: Английский

---

Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 10037 - 10037

Published: Sept. 2, 2022

Aerobic glycolysis is an emerging hallmark of many human cancers, as cancer cells are defined a “metabolically abnormal system”. Carbohydrates metabolically reprogrammed by its metabolizing and catabolizing enzymes in such cells. Normal acquire their energy from oxidative phosphorylation, while glycolysis, known the “Warburg effect”. Energy–metabolic differences easily found growth, invasion, immune escape anti-tumor drug resistance The pathway carried out multiple enzymatic steps yields two pyruvate molecules one glucose (Glc) molecule orchestral reaction enzymes. Uncontrolled or abnormally activated observed metabolism with enhanced levels glycolytic proteins activities. In effect”, tumor utilize supplied lactic acid-based fermentative operated glycolysis-specific hexokinase (HK), keto-HK-A, Glc-6-phosphate isomerase, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase, phosphofructokinase (PFK), phosphor-Glc isomerase (PGI), fructose-bisphosphate aldolase, phosphoglycerate (PG) kinase (PGK)1, triose phosphate PG mutase (PGAM), glyceraldehyde-3-phosphate dehydrogenase, enolase, isozyme type M2 (PKM2), dehydrogenase (PDH), PDH lactate dehydrogenase. They related to flux. key involved directly linked oncogenesis resistance. Among metabolic enzymes, PKM2, PGK1, HK, keto-HK-A nucleoside diphosphate also have protein Because glycolysis-generated not enough, cell-favored produce low ATP level seems be non-efficient for growth self-protection. Thus, Warburg effect still attractive phenomenon understand favored cancer. If basic properties effect, including genetic mutations signaling shifts considered, anti-cancer therapeutic targets can raised. Specific therapeutics targeting aerobic hypoxic microenvironments been developed kill present review deals tumor-specific revisited viewpoint recent progress.

Language: Английский

---

Cancer-associated fibroblast-specific lncRNA LINC01614 enhances glutamine uptake in lung adenocarcinoma

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Oct. 8, 2022

Abstract Background Besides featured glucose consumption, recent studies reveal that cancer cells might prefer “addicting” specific energy substrates from the tumor microenvironment (TME); however, underlying mechanisms remain unclear. Methods Fibroblast-specific long noncoding RNAs were screened using RNA-seq data of our NJLCC cohort, TCGA, and CCLE datasets. The expression package LINC01614 into exosomes identified flow cytometric sorting, fluorescence in situ hybridization (FISH), quantitative reverse transcription polymerase chain reaction (RT-PCR). transfer functional role lung adenocarcinoma (LUAD) CAFs investigated 4-thiouracil-labeled RNA gain- loss-of-function approaches. pull-down, immunoprecipitation, dual-luciferase assay, gene microarray, bioinformatics analysis performed to investigate involved. Results We demonstrate cancer-associated fibroblasts (CAFs) LUAD primarily enhance glutamine metabolism cells. A CAF-specific RNA, LINC01614, packaged by CAF-derived exosomes, mediates enhancement uptake Mechanistically, directly interacts with ANXA2 p65 facilitate activation NF-κB, which leads upregulation transporters SLC38A2 SLC7A5 eventually enhances influx Reciprocally, tumor-derived proinflammatory cytokines upregulate CAFs, constituting a feedforward loop between Blocking exosome-transmitted inhibits addiction growth vivo. Clinically, is associated poor prognosis patients LUAD. Conclusion Our study highlights therapeutic potential targeting lncRNA inhibit utilization progression

Language: Английский

---

Insulin/IGF Axis and the Receptor for Advanced Glycation End Products: Role in Meta-inflammation and Potential in Cancer Therapy

Endocrine Reviews, Journal Year: 2023, Volume and Issue: 44(4), P. 693 - 723

Published: March 4, 2023

Abstract In metabolic conditions such as obesity and diabetes, which are associated with deregulated signaling of the insulin/insulin-like growth factor system (IIGFs), inflammation plays a dominant role. cancer, IIGFs is implicated in disease progression, particularly during diabetes; however, further mediators may act concert to trigger meta-inflammation. The receptor for advanced glycation end-products (RAGE) its ligands bridge together metabolism obesity, cancer. Herein, we summarize main mechanisms meta-inflammation malignancies provide our readers most recent understanding conceptual advances on role RAGE at crossroad between impaired inflammation, toward aggressiveness. We inform potential hubs cross-communications driven by aberrant axis dysfunctional tumor microenvironment. Furthermore, offer rationalized view opportunity terminate via targeting pathway, possibility shut molecular connections IIGFs, better control diabetes- obesity-associated cancers.

Language: Английский

---

Critical roles and clinical perspectives of RNA methylation in cancer

MedComm, Journal Year: 2024, Volume and Issue: 5(5)

Published: May 1, 2024

Abstract RNA modification, especially methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all modifications. It plays significant role in metabolism, affecting processing, stability, translation, thereby modulating gene expression cell essential proliferation, survival, metastasis. Increasing studies have revealed the disruption metabolism mediated by methylation has been implicated various aspects cancer particularly metabolic reprogramming immunity. This profound implications tumor growth, metastasis, therapy response. Herein, we elucidate fundamental characteristics their impact on expression. We highlight intricate relationship between reprogramming, immunity, using well‐characterized phenomenon as framework to discuss methylation's specific roles mechanisms progression. Furthermore, explore potential targeting regulators novel approach therapy. By underscoring complex which contributes this review provides foundation developing new prognostic markers therapeutic strategies aimed at treatment.

Language: Английский

---

Folate-targeted nanoparticles for glutamine metabolism inhibition enhance anti-tumor immunity and suppress tumor growth in ovarian cancer

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 379, P. 89 - 104

Published: Jan. 8, 2025

Language: Английский

---

Anticancer Attributes and Multifaceted Pharmacological Implications of Laetrile and Amygdalin

Cell Biology International, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

ABSTRACT Laetrile, known as vitamin B17, is often used interchangeably with amygdalin. Laetrile a semi‐synthesis product of amygdalin, whereas amygdalin naturally occurring substance in many plants. Both compounds have nitrile functional group that, when activated by the intestinal enzyme β‐glucosidases, releases hydrogen cyanide. The two been considered for long time alternative therapy cancer treatment however, findings available literature are discordant on real efficacy laetrile/amygdalin cancer, highlighting negative benefit‐risk ratio. In this regard, study aimed to comprehensively analyze scientific data laetrile/amygdalin, special emphasis their pharmacokinetics, underlying pharmacological properties, mode action potent antitumor agent, and effect human health. results showed that there no clear evidence following administration, especially at clinical trial level. However, vitro studies biological activity these positive effects related antifibrotic, anti‐inflammatory, antiasthmatic, immunoregulatory processes. Laetrile's mechanism closely resembles affecting signaling pathways. due its cyanide toxicity, it was banned food drug administration (FDA) safety concerns. Despite not receiving permission from FDA, laetrile emerged an 1970s. Nonetheless, continuing research investigating safer methods activating targeted treatment. This opens interesting prospects using medical therapies, which, further needed.

Language: Английский

---

Current Status and Future Perspectives of Lactate Dehydrogenase Detection and Medical Implications: A Review

Biosensors, Journal Year: 2022, Volume and Issue: 12(12), P. 1145 - 1145

Published: Dec. 7, 2022

The demand for glucose uptake and the accompanying enhanced glycolytic energy metabolism is one of most important features cancer cells. Unlike aerobic metabolic pathway in normal cells, large amount pyruvate produced by dramatic increase glycolysis cells needs to be converted lactate cytoplasm, which cannot done without a dehydrogenase (LDH). This explains why elevated serum LDH concentrations are usually seen patient populations. not only correlates with clinical prognostic survival indicators, but also guides subsequent drug therapy. Besides their role cancers, biomarker malaria other diseases. Therefore, it urgent develop methods sensitive convenient detection. Here, this review systematically summarizes impact detection principles advantages as well limitations different future trends were discussed.

Language: Английский

---

Bladder Cancer‐Derived Small Extracellular Vesicles Promote Tumor Angiogenesis by Inducing HBP‐Related Metabolic Reprogramming and SerRS O‐GlcNAcylation in Endothelial Cells

Advanced Science, Journal Year: 2022, Volume and Issue: 9(30)

Published: Aug. 31, 2022

Abstract A malformed tumour vascular network provokes the nutrient‐deprived microenvironment (TME), which conversely activates endothelial cell (EC) functions and stimulates neovascularization. Emerging evidence suggests that flexible metabolic adaptability of cells helps to establish a symbiosis among various subpopulations in fluctuating TME. In this study, authors propose novel link between bladder cancer (BCa) ECs nutrient‐scarce TME, BCa‐secreted glutamine‐fructose‐6‐phosphate aminotransferase 1 (GFAT1) via small extracellular vesicles (sEVs) reprograms glucose metabolism by increasing hexosamine biosynthesis pathway flux thus enhances O‐GlcNAcylation. Moreover, seryl‐tRNA synthetase (SerRS) O‐GlcNAcylation at serine 101 promotes its degradation ubiquitination impeded importin α 5‐mediated nuclear translocation. Intranuclear SerRS attenuates growth factor transcription competitively binding GC‐rich region proximal promotor. Additionally, GFAT1 knockout blocks angiogenesis both vitro vivo. However, administration GFAT1‐overexpressing BCa cells‐derived sEVs increase angiogenetic activity GFAT1‐knockout mice. summary, study inhibiting sEV‐mediated secretion from targeting may serve as strategies for antiangiogenetic therapy.

Language: Английский

---

Involvement of ACACA (acetyl-CoA carboxylase α) in the lung pre-metastatic niche formation in breast cancer by senescence phenotypic conversion in fibroblasts

Cellular Oncology, Journal Year: 2023, Volume and Issue: 46(3), P. 643 - 660

Published: Jan. 6, 2023

Reprogramming of metabolism is strongly associated with the development cancer. However, role metabolic reprogramming in remodeling pre-metastatic niche (PMN), a key step metastasis, still unknown. We aimed to investigate alternation during lung PMN formation breast cancer.We assessed transcriptomes and lipidomics MMTV-PyVT mice by microarray liquid chromatography-tandem mass spectrometry before metastasis. The validation gene or protein expressions was performed quantitative real-time polymerase chain reaction immunoblot immunohistochemistry respectively. fibroblasts were isolated from then co-cultured cancer identify influence on change PMN.We demonstrated changes lipid profile several genes lungs cancer-bearing spreading. expression ACACA (acetyl-CoA carboxylase α) downregulated fibroblasts, which contributed acetylation protein's lysine residues synthesis fatty acid. downregulation triggered senescent inflammatory phenotypic shift both vivo vitro models. senescence-associated secretory phenotype enabled recruitment immunosuppressive granulocytic myeloid-derived suppressor cells into through production CXCL1 lungs. Knock-in prevented metastasis mouse model, further supporting that involved PMN.Taken together, these data revealed mechanism directed an

Language: Английский

---