The EACR’s Top 10 Cancer Research Publications is a regular summary of the most interesting and impactful recent papers in cancer research. It is 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.
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Pascual, G., Domínguez, D., Elosúa-Bayes, M. et al. Nature 599, 485–490 (2021).
Summary of the findings
Fatty acid uptake and an altered metabolism are hallmarks of metastasis. In this work, we describe how dietary palmitic acid (and not oleic or linoleic acids) induces a more aggressive profile in tumour cells and how this remains as a form of cellular “memory”. Tumours from mice fed a short-term diet rich in palm oil and tumour cells
briefly exposed to palmitic acid in vitro remained highly metastatic even after being
successively transplanted (without further exposure to high levels of this fatty acid).
The prometastatic profile is related to the capacity of the tumour cells to establish a neural network around the tumour. The palmitic acid-induced prometastatic memory, which is dependent on the fatty acid transporter CD36, the transcription factor EGR2 and the glial-cell-stimulating peptide galanin, promotes a pro-regenerative state of tumour-activated Schwann cells, which secrete a specialized extracellular matrix. Intratumoural Schwann cells and innervation are parameters that strongly correlate with metastasis.
Using a variety of approaches to block the formation of the neural network surrounding the tumour, we were able to prevent the development of metastases.
Future impact of the findings
Our findings provide a novel insight into the metastasis initiation process and may drive new approaches to tackle cancer. In this regard, the mechanisms detailed in our work pave the way for the development of therapies that specifically block metastasis, which is the main cause of death by cancer.
