Glycogen synthase kinase-3: A potential preventive target for prostate cancer management

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• 作者：Benyi Li ; M.D. ; Ph.D.^a ; ^{bli@kumc.edu" class="auth_mail" title="E-mail the corresponding author} ; James Brantley Thrasher ; M.D.^a ; Paul Terranova ; Ph.D.^b ; ^c
• 关键词：GSK-3 ; Small chemicals ; Prostate cancer ; Lithium chloride ; Cancer prevention and treatment
• 刊名：Urologic Oncology: Seminars and Original Investigations
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：33
• 期：11
• 页码：456-463
• 全文大小：302 K

文摘

Prostate cancers are the frequently diagnosed cancers in men, and patients with metastatic disease only have 28% chance for 5-year survival. Patients with low-risk tumors are subjected to active surveillance, whereas high-risk cases are actively treated. Unfortunately, there is no cure for patients with late-stage disease. Glycogen synthase kinase-3 (GSK-3, 伪 and 尾) is a protein serine/threonine kinase and has diverse cellular functions and numerous substrates. We sought to summarize all the studies done with GSK-3 in prostate cancers and to provide a prospective direction for future work.

Methods and materials

A comprehensive search of the literature on the electronic databases PubMed was conducted for the subject terms of GSK-3 and prostate cancer. Gene mutation and expression information was extracted from Oncomine and COSMIC databases. Case reports were not included.

Results

Accumulating evidence indicates that GSK-3伪 is mainly expressed in low-risk prostate cancers and is related to hormone-dependent androgen receptor (AR)–mediated gene expression, whereas GSK-3尾 is mainly expressed in high-risk prostate cancers and is related to hormone-independent AR-mediated gene expression. GSK-3 has been demonstrated as a positive regulator in AR transactivation and prostate cancer growth independent of the Wnt/尾-catenin pathway. Different types of GSK-3inhibitors including lithium show promising results in suppressing tumor growth in different animal models of prostate cancer. Importantly, clinical use of lithium is associated with reduced cancer incidence in psychiatric patients.

Conclusions

Taken together, GSK-3 inhibition might be implicated in prostate cancer management as a preventive treatment.