Abstract
The Warburg effect in tumour cells is associated with the upregulation of glycolysis to generate ATP, even under normoxic conditions and the presence of fully functioning mitochondria. However, scientific advances made over the past 15 years have reformed this perspective, demonstrating the importance of oxidative phosphorylation (OXPHOS) as well as glycolysis in malignant cells. The metabolic phenotypes in melanoma display heterogeneic dynamism (metabolic plasticity) between glycolysis and OXPHOS, conferring a survival advantage to adapt to harsh conditions and pathways of chemoresistance. Furthermore, the simultaneous upregulation of both OXPHOS and glycolysis (metabolic symbiosis) has been shown to be vital for melanoma progression. The tumour microenvironment (TME) has an essential supporting role in promoting progression, invasion and metastasis of melanoma. Mesenchymal stromal cells (MSCs) in the TME show a symbiotic relationship with melanoma, protecting tumour cells from apoptosis and conferring chemoresistance. With the significant role of OXPHOS in metabolic plasticity and symbiosis, our review outlines how mitochondrial transfer from MSCs to melanoma tumour cells plays a key role in melanoma progression and is the mechanism by which melanoma cells regain OXPHOS capacity even in the presence of mitochondrial mutations. The studies outlined in this review indicate that targeting mitochondrial trafficking is a potential novel therapeutic approach for this highly refractory disease.
Original language | English |
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Pages (from-to) | 115-123 |
Number of pages | 9 |
Journal | British Journal of Cancer |
Volume | 124 |
Issue number | 1 |
Early online date | 18 Nov 2020 |
DOIs | |
Publication status | Published - 5 Jan 2021 |
Profiles
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Kristian Bowles
- Norwich Medical School - Dean of Norwich Medical School
- Cancer Studies - Member
Person: Research Group Member, Academic, Teaching & Research
-
Stuart Rushworth
- Norwich Medical School - Professor
- Metabolic Health - Director
- Cancer Studies - Member
Person: Research Group Member, Academic, Teaching & Research