Disrupting the 'Warburg effect' re-routes cancer cells to OXPHOS offering a vulnerability point via 'ferroptosis'-induced cell death.

Adv Biol Regul

Université Côte d'Azur, Institute for Research on Cancer and Aging (IRCAN), CNRS, INSERM, Centre A. Lacassagne, 33 avenue de Valombrose, Nice, France; Medical Biology Department, Centre Scientifique de Monaco (CSM), Monaco. Electronic address:

Published: May 2018

The evolution of life from extreme hypoxic environments to an oxygen-rich atmosphere has progressively selected for successful metabolic, enzymatic and bioenergetic networks through which a myriad of organisms survive the most extreme environmental conditions. From the two lethal environments anoxia/high O, cells have developed survival strategies through expression of the transcriptional factors ATF4, HIF1 and NRF2. Cancer cells largely exploit these factors to thrive and resist therapies. In this review, we report and discuss the potential therapeutic benefit of disrupting the major Myc/Hypoxia-induced metabolic pathway, also known as fermentative glycolysis or "Warburg effect", in aggressive cancer cell lines. With three examples of genetic disruption of this pathway: glucose-6-phosphate isomerase (GPI), lactate dehydrogenases (LDHA and B) and lactic acid transporters (MCT1, MCT4), we illuminate how cancer cells exploit metabolic plasticity to survive the metabolic and energetic blockade or arrest their growth. In this context of NRF2 contribution to OXPHOS re-activation we will show and discuss how, by disruption of the cystine transporter xCT (SLC7A11), we can exploit the acute lethal phospholipid peroxidation pathway to induce cancer cell death by 'ferroptosis'.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbior.2017.12.002DOI Listing

Publication Analysis

Top Keywords

cancer cells
12
cell death
8
cells exploit
8
cancer cell
8
cancer
5
disrupting 'warburg
4
'warburg effect'
4
effect' re-routes
4
re-routes cancer
4
cells
4

Similar Publications

Targeting p38γ synergistically enhances sorafenib-induced cytotoxicity in hepatocellular carcinoma.

Cell Biol Toxicol

January 2025

Division of Abdominal Tumor Multimodality Treatment, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan Province, China.

Sorafenib (Sora) is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC). It can significantly improve the survival rate of patients with advanced HCC, but it is prone to drug resistance during treatment, so the therapeutic effect is extremely limited. Here, we demonstrate that an elevated expression of protein kinase p38γ in hepatocellular carcinoma cells diminishes the tumor cells' sensitivity to Sora.

View Article and Find Full Text PDF

Effect of terahertz radiation on cells and cellular structures.

Front Optoelectron

January 2025

Institute of Physics, Saratov State University, Saratov, 410012, Russia.

The paper presents the results of modern research on the effects of electromagnetic terahertz radiation in the frequency range 0.5-100 THz at different levels of power density and exposure time on the viability of normal and cancer cells. As an accompanying tool for monitoring the effect of radiation on biological cells and tissues, spectroscopic research methods in the terahertz frequency range are described, and attention is focused on the possibility of using the spectra of interstitial water as a marker of pathological processes.

View Article and Find Full Text PDF

Background: Marathon training and running have many beneficial effects on human health and physical fitness; however, they also pose risks. To date, no comprehensive review regarding both the benefits and risks of marathon running on different organ systems has been published.

Main Body: The aim of this review was to provide a comprehensive review of the benefits and risks of marathon training and racing on different organ systems.

View Article and Find Full Text PDF

Unveiling the role of PANoptosis-related genes in breast cancer: an integrated study by multi-omics analysis and machine learning algorithms.

Breast Cancer Res Treat

January 2025

Department of Breast Surgery, Thyroid Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, No.141, Tianjin Road, Huangshi, 435000, Hubei, China.

Background: The heterogeneity of breast cancer (BC) necessitates the identification of novel subtypes and prognostic models to enhance patient stratification and treatment strategies. This study aims to identify novel BC subtypes based on PANoptosis-related genes (PRGs) and construct a robust prognostic model to guide individualized treatment strategies.

Methods: The transcriptome data along with clinical data of BC patients were sourced from the TCGA and GEO databases.

View Article and Find Full Text PDF

Targeted editing of CCL5 with CRISPR-Cas9 nanoparticles enhances breast cancer immunotherapy.

Apoptosis

January 2025

Department of Breast Cancer Surgery, Jiangxi Cancer Hospital & Institute, Jiangxi Clinical Research Center for Cancer, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Key Laboratory of Oncology, No. 519 Beijing East Road, Nanchang, Jiangxi, 330029, China.

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Immunotherapy, a promising therapeutic approach, often faces challenges due to the immunosuppressive tumor microenvironment. This study explores the innovative use of CRISPR-Cas9 technology in conjunction with FCPCV nanoparticles to target and edit the C-C Motif Chemokine Ligand 5 (CCL5) gene, aiming to improve the efficacy of breast cancer immunotherapy.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!