School of Life Sciences, Faculty of Science, University of Technology Sydney, 15 Broadway, Ultimo, Sydney, NSW, 2007, Australia.
Central Laboratory, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China.
Mol Cancer. 2018 Feb 19;17(1):37. doi: 10.1186/s12943-018-0803-3.
Regulation of the PI-3 kinase (PI3K)/Akt signalling pathway is essential for maintaining the integrity of fundamental cellular processes, cell growth, survival, death and metabolism, and dysregulation of this pathway is implicated in the development and progression of cancers. Receptor tyrosine kinases (RTKs) are major upstream regulators of PI3K/Akt signalling. The phosphatase and tensin homologue (PTEN), a well characterised tumour suppressor, is a prime antagonist of PI3K and therefore a negative regulator of this pathway. Loss or inactivation of PTEN, which occurs in many tumour types, leads to overactivation of RTK/PI3K/Akt signalling driving tumourigenesis. Cellular PTEN levels are tightly regulated by a number of transcriptional, post-transcriptional and post-translational regulatory mechanisms. Of particular interest, transcription of the PTEN pseudogene, PTENP1, produces sense and antisense transcripts that exhibit post-transcriptional and transcriptional modulation of PTEN expression respectively. These additional levels of regulatory complexity governing PTEN expression add to the overall intricacies of the regulation of RTK/PI-3 K/Akt signalling. This review will discuss the regulation of oncogenic PI3K signalling by PTEN (the regulator) with a focus on the modulatory effects of the sense and antisense transcripts of PTENP1 on PTEN expression, and will further explore the potential for new therapeutic opportunities in cancer treatment.
PI-3 激酶（PI3K）/Akt 信号通路的调节对于维持基本细胞过程、细胞生长、存活、死亡和代谢的完整性至关重要，该通路的失调与癌症的发生和发展有关。受体酪氨酸激酶（RTKs）是 PI3K/Akt 信号的主要上游调节剂。磷酸酶和张力蛋白同源物（PTEN）是一种特征明确的肿瘤抑制因子，是 PI3K 的主要拮抗剂，因此是该通路的负调节剂。在许多肿瘤类型中都会发生 PTEN 的缺失或失活，从而导致 RTK/PI3K/Akt 信号的过度激活，驱动肿瘤发生。细胞内的 PTEN 水平受到许多转录、转录后和翻译后调节机制的严格调控。特别值得注意的是，PTEN 假基因 PTENP1 的转录产生了分别表现出 PTEN 表达转录后和转录调节的 sense 和 antisense 转录本。这些额外的 PTEN 表达调控层次增加了 RTK/PI-3K/Akt 信号调节的整体复杂性。本文综述了 PTEN（调节剂）对致癌性 PI3K 信号的调节，重点讨论了 PTENP1 的 sense 和 antisense 转录本对 PTEN 表达的调节作用，并进一步探讨了在癌症治疗中开辟新的治疗机会的潜力。
