Untangling the role of tau in sex hormone responsive cancers: lessons learnt from Alzheimer's disease

Abstract 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.