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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Padmanaban, V. et al. Nature. 633: 207–215 (2024).
doi: 10.1038/s41586-024-07767-5.
Summary and graphical abstract by Alexandra Boitor, EACR Scientific Officer
Summary of the findings
It has been known for decades that tumours are innervated by the peripheral nervous system. Whilst this is a growing field of research, and more and more aspects of cancer neurobiology are being described in the literature, there are still caveats in our knowledge. One such poorly understood aspect is the role that sensory innervation plays in breast cancer metastasis.
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The authors of this paper build on their previous work that identified overexpression of the axon-guidance protein SLIT2 in the endothelium of metastatic breast tumours as a driver of metastasis. In this paper, Padmanaban et al., show that SLIT 2 drives breast tumour innervation, and that increased sensory innervation in tumours drives cell proliferation and metastasis in breast cancer. In this study, the pro-metastatic effects were driven by neuronal SP secretion in the tumour microenvironment. The authors propose a model through which SP induces apoptosis in a subpopulation of cancer cells that express TACR1, leading to ssRNA release in the tumour microenvironment. The ssRNA released interacts with TLR7 on the surface of remaining tumour cells and mediates the pro-proliferative and pro-invasive behaviour in an immune-independent fashion, likely activating non-canonical PI3K signalling downstream of TLR. The authors also provide a proof-of-concept for therapeutic targeting: aprepitant, a drug used to treat nausea that acts as an antagonist of TACR1, showed the ability to inhibit tumour growth and metastatic progression in cell culture and PDX models.
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