Valencia et al. investigated the role of p62 in tumour-associated stromal cells, in which its expression is frequently reduced in tumour samples. The growth of prostate cancer cells in syngeneic p62-knockout mice was significantly increased compared to growth in control mice. p62 loss in cancer-associated fibroblasts led to increased expression of interleukin-6 (IL-6), the loss of which reversed the effects of p62 ablation, indicating that p62 suppresses the expression of IL-6, which, when expressed by fibroblasts, has paracrine effects on tumour cells. Notably, p62 repressed mTOR complex 1, MYC and the production of reactive oxygen species through metabolic reprogramming, which in turn repressed the expression of IL-6.
References
Valencia, T. et al. Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis. Cancer Cell http://dx.doi.org/10.1016/j.ccr.2014.05.004 (2014)
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Alderton, G. Stromal metabolism has paracrine effects. Nat Rev Cancer 14, 515 (2014). https://doi.org/10.1038/nrc3794
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DOI: https://doi.org/10.1038/nrc3794
