Crosstalk between the Warburg effect, redox regulation and autophagy induction in tumourigenesis

Abstract

Tumourigenic tissue uses modified metabolic signalling pathways in order to support hyperproliferation and survival. Cancer-associated aerobic glycolysis resulting in lactic acid production was described nearly 100 years ago. Furthermore, increased reactive oxygen species (ROS) and lactate quantities increase metabolic, survival and proliferation signalling, resulting in increased tumourigenesis. In order to maintain redox balance, the cell possesses innate antioxidant defence systems such as superoxide dismutase, catalase and glutathione. Several stimuli including cells deprived of nutrients or failure of antioxidant systems result in oxidative stress and cell death induction. Among the cell death machinery is autophagy, a compensatory mechanism whereby energy is produced from damaged and/or redundant organelles and proteins, which prevents the accumulation of waste products, thereby maintaining homeostasis. Furthermore, autophagy is maintained by several pathways including phosphoinositol 3 kinases, the mitogen-activated protein kinase family, hypoxia-inducible factor, avian myelocytomatosis viral oncogene homolog and protein kinase receptor-like endoplasmic reticulum kinase. The persistent potential of cancer metabolism, redox regulation and the crosstalk with autophagy in scientific investigation pertains to its ability to uncover essential aspects of tumourigenic transformation. This may result in clinical translational possibilities to exploit tumourigenic oxidative status and autophagy to advance our capabilities to diagnose, monitor and treat cancer.

Plasma metabolites related to cellular energy metabolism are altered in adults with Down syndrome and Alzheimer's disease

“…Literature has also recently described molecular cross-talk between the Warburg effect, redox homeostasis, and autophagy induction-all processes proposed as potential drivers of AD (Tonnies & Trushina, 2017;Uddin et al, 2018;Vlassenko & Raichle, 2015). To the extent that this crosstalk is mediated by known pathways such as phosphatidylinositol-3-kinase/ protein kinase B (PI3K/Akt) activation, mammalian target of rapamycin (mTOR) signal transduction, and mitogen-activated protein kinase (MAPK) activity (Gwangwa, Joubert, & Visagie, 2018), their role in integrating pro-survival versus pro-apoptotic signaling in DS-AD should be further evaluated, ideally in neural tissue.…”

Ferroptosis in Cancer Cell Biology

“…This metabolic re-programming in cancer was famously discovered by Warburg and Cori in the 1920s [8,9] and has been suggested as a cancer cell means to evade toxic levels of ROS production. However, maintenance of this Warburg effect requires higher glucose uptake and elevated metabolic activity making tumour cells nevertheless heavily reliant on the antioxidant machinery and maybe even more susceptible to oxidative stress [10,11]. Therefore, highly proliferative cancer cells are known to require handling of elevated cellular ROS levels in order to successfully establish tumours [12][13][14].…”

shRNA Glut-1 inhibits cell viability, apoptosis and migration of laryngeal carcinoma HEp-2 cells through regulating Beclin-1-mediated autophagy

“…Preliminary studies have shown that autophagy through Glut-1 translocation affects glucose uptake of cancer cells [19][20][21][22][23]. In comparison with normal cells, cancer cells preferentially produce energy by glycolysis in anaerobic environments [4]. The energy supply of cancer cells in hypoxic environments is related to the high-level expression of Glut-1 and autophagy.…”

“…Laryngeal squamous cell carcinoma (LSCC), which is related to many risk factors, including smoking, drinking alcohol, and laryngeal reflux, is one of the most common malignant tumors occurring in the head and neck [1]. Some studies have demonstrated that autophagy and glucose metabolism play important roles in the occurrence and development of cancer cells [2][3][4][5]. However, the mechanisms underlying autophagy and glucose metabolism in the process of LSCC remain unclear.…”

“…It has gradually become apparent that most tumor cells show a variable glycolysis phenotype, so increased glycolytic metabolism has been identified as a characteristic of malignant cells, known as the Warburg effect [4]. Previous studies confirmed the upregulation of members of the glucose transporter family (Gluts) during the process of glycolysis in tumor cells to meet the energy needs of cancer cells [6][7][8].…”