Cancer Endocrinology Group, Learning & Research Building, Southmead Hospital, Translational Health Sciences, Bristol Medical School, Bristol BS10 5NB, UK.
Department of Urology, Bristol Urological Institute, Southmead Hospital, Bristol BS10 5NB, UK.
Clin Sci (Lond). 2024 Nov 6;138(21):1357-1369. doi: 10.1042/CS20230317.
Tubulin associated unit has been extensively studied in neurodegenerative diseases including Alzheimer's disease (AD), whereby its hyperphosphorylation and accumulation contributes to disease pathogenesis. Tau is abundantly expressed in the central nervous system but is also present in non-neuronal tissues and in tumours including sex hormone responsive cancers such as breast and prostate. Curiously, hormonal effects on tau also exist in an AD context from numerous studies on menopause, hormone replacement therapy, and androgen deprivation therapy. Despite sharing some risk factors, most importantly advancing age, there are numerous reports from population studies of, currently poorly explained inverse associations between cancer and Alzheimer's disease. We previously reviewed important components of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) signalling pathway and their differential modulation in relation to the two diseases. Similarly, receptor tyrosine kinases, estrogen receptor and androgen receptor have all been implicated in the pathogenesis of both cancer and AD. In this review, we focus on tau and its effects in hormone responsive cancer in terms of development, progression, and treatment and in relation to sex hormones and PI3K/Akt signalling molecules including IRS-1, PTEN, Pin1, and p53.
微管相关蛋白在神经退行性疾病中被广泛研究，包括阿尔茨海默病（AD），其过度磷酸化和积累有助于疾病的发病机制。Tau 在中枢神经系统中大量表达，但也存在于非神经元组织和肿瘤中，包括性激素反应性癌症，如乳腺癌和前列腺癌。奇怪的是，许多关于绝经、激素替代疗法和雄激素剥夺疗法的 AD 研究也存在激素对 Tau 的影响。尽管存在一些共同的危险因素，最重要的是年龄的增长，但目前有大量来自人群研究的报告表明，癌症和阿尔茨海默病之间存在着许多难以解释的负相关关系。我们之前回顾了磷酸肌醇-3-激酶/蛋白激酶 B（PI3K/Akt）信号通路的重要组成部分及其与两种疾病的差异调节。同样，受体酪氨酸激酶、雌激素受体和雄激素受体都与癌症和 AD 的发病机制有关。在这篇综述中，我们重点关注 Tau 及其在激素反应性癌症中的作用，包括其在癌症发展、进展和治疗中的作用，以及与性激素和 PI3K/Akt 信号分子（包括 IRS-1、PTEN、Pin1 和 p53）的关系。
