Chow Jonathan Tak-Sum, Salmena Leonardo
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Fac Rev. 2020 Dec 23;9:31. doi: 10.12703/r/9-31. eCollection 2020.
In over two decades since the discovery of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), nearly 18,000 publications have attempted to elucidate its functions and roles in normal physiology and disease. The frequent disruption of PTEN in cancer cells was a strong indication that it had critical roles in tumour suppression. Germline mutations have been identified in patients with heterogeneous tumour syndromic diseases, known as PTEN hamartoma tumour syndrome (PHTS), and in some individuals with autism spectrum disorders (ASD). Today we know that by limiting oncogenic signalling through the phosphoinositide 3-kinase (PI3K) pathway, PTEN governs a number of processes including survival, proliferation, energy metabolism, and cellular architecture. Some of the most exciting recent advances in the understanding of PTEN biology and signalling have revisited its unappreciated roles as a protein phosphatase, identified non-enzymatic scaffold functions, and unravelled its nuclear function. These discoveries are certain to provide a new perspective on its full tumour suppressor potential, and knowledge from this work will lead to new anti-cancer strategies that exploit PTEN biology. In this review, we will highlight some outstanding questions and some of the very latest advances in the understanding of the tumour suppressor PTEN.
自10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）被发现后的二十多年里，近18,000篇出版物试图阐明其在正常生理和疾病中的功能及作用。癌细胞中PTEN的频繁破坏有力地表明它在肿瘤抑制中起关键作用。在患有称为PTEN错构瘤肿瘤综合征（PHTS）的异质性肿瘤综合征疾病的患者以及一些患有自闭症谱系障碍（ASD）的个体中已鉴定出种系突变。如今我们知道，通过限制磷脂酰肌醇3激酶（PI3K）途径的致癌信号传导，PTEN控制着包括存活、增殖、能量代谢和细胞结构在内的许多过程。最近在对PTEN生物学和信号传导的理解方面取得的一些最令人兴奋的进展重新审视了其作为蛋白磷酸酶未被重视的作用，确定了非酶支架功能，并揭示了其核功能。这些发现肯定会为其完整的肿瘤抑制潜力提供新的视角，并且这项工作的知识将导致利用PTEN生物学的新抗癌策略。在这篇综述中，我们将重点介绍一些关于肿瘤抑制因子PTEN理解方面的突出问题和一些最新进展。
