A research group led by Assistant Professor Hideaki Takahashi of Yokohama City University and Dr. Moran Amit of the MD Anderson Cancer Center in the United States found that cancer cells that have lost the function of the cancer suppressor gene p53 change the surrounding sensory nerves into sympathetic nerves. , Discovered that the sympathetic nerve promotes the development of cancer, and published it in the English scientific journal "Nature".

 Cancer cells change the surrounding environment (cancer microenvironment) in favor of cancer progression.In recent years, therapeutic methods such as angiogenesis inhibitors and immune checkpoint inhibitors targeting this cancer microenvironment have been put into practical use.On the other hand, recent studies have revealed the involvement of sympathetic nerves in cancer progression in the cancer microenvironment, but the origin of the sympathetic nerves and the mechanism of interaction between cancer cells and nerves have not been clarified.

 This research group comprehensively analyzes gene mutations and gene expression in squamous cell carcinoma of the head and neck.As a result, it was found that the survival time of patients is short when the density of nerve fibers in cancer tissue is high.Next, we elucidated the mechanism by which the loss of p53 function increases nerve density.Loss of p53 function in cancer cells was thought to increase nerve density in cancer tissues through decreased expression of tumor suppressor microRNAs (miR-34a) in extracellular vesicles.

 In addition, extracellular vesicles derived from cancer cells that have lost p53 activate intracellular signal transduction pathways involved in nerve fiber proliferation, and further, stem cell-like properties of nerve cells and noradrenaline released from the ends of sympathetic nerves. It was found that the pathways involved in the synthesis of vesicles were also activated.It was also shown that the sympathetic nerves that proliferated in the tissues surrounding the cancer were derived from the lingual nerve, which is a sensory nerve, rather than the original sympathetic nerve.

 The results of this study show that cancer-related sympathetic nerves can be a promising therapeutic target in addition to being a predictor of patient prognosis.

Paper information:[Nature] Loss of p53 drives neuron reprogramming in head and neck cancer

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