The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors unless otherwise indicated.
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Mangalhara, K. C., Varanasi, S. K., et al. Science 381, pages 1316-1323 (2023).
doi: doi.org/10.1126/science.abq1053.
Summary and graphical abstract by Alexandra Boitor, EACR Scientific Officer
Summary of the findings
Summary of the findingsCancer growth relies on metabolic plasticity, which is provided, in part, by the mitochondrial tricarboxylic acid cycle and electron transport chain.
In this paper, the authors looked at how this could be leveraged to hinder cancer progression.
Mangalhara, Varanasi et al. noticed that the knockdown of the electron transport chain complex C II in melanoma cells leads to a
substantial decrease in tumour growth. Lack of complex C II induces accumulation of mitochondrial succinate which in turn modulates the tumour epigenetic landscape leading to changes in protein transcription. As a consequence, MHC-I antigen presentation is increased leading to a strong antitumour immune response carried by CD8+ T cells. Further on, the authors of this pa
per investigated if rewiring of the electron transport chain towards favouring the use of complex C I over complex C II could increase
succinate levels to a level that would trigger an anti-tumoral immune reaction, whilst maintaining the electron chain activity and ATP production. Knockout of methylation-controlled J protein (MCJ), a protein from the mitochondrial inner membrane that endogenously interacts with C I, leads to reduced C II activity and subsequent increase in succinate levels, culminating in decreased tumour growth due to immune cell infiltration. These results indicate that discrete rewiring of the electron transport chain could be considered for turning cold tumours hot and hence improving immunotherapy efficiency.
