Fedorova Olga, Parfenyev Sergey, Daks Alexandra, Shuvalov Oleg, Barlev Nickolai A
Institute of Cytology RAS, 194064 St. Petersburg, Russia.
Cancers (Basel). 2022 Aug 3;14(15):3786. doi: 10.3390/cancers14153786.
Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN) is one of the critical tumor suppressor genes and the main negative regulator of the PI3K pathway. PTEN is frequently found to be inactivated, either partially or fully, in various malignancies. The PI3K/AKT pathway is considered to be one of the main signaling cues that drives the proliferation of cells. Perhaps it is not surprising, then, that this pathway is hyperactivated in highly proliferative tumors. Importantly, the PI3K/AKT pathway also coordinates the epithelial-mesenchymal transition (EMT), which is pivotal for the initiation of metastases and hence is regarded as an attractive target for the treatment of metastatic cancer. It was shown that PTEN suppresses EMT, although the exact mechanism of this effect is still not fully understood. This review is an attempt to systematize the published information on the role of PTEN in the development of malignant tumors, with a main focus on the regulation of the PI3K/AKT pathway in EMT.
10号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)是关键的肿瘤抑制基因之一,也是PI3K通路的主要负调节因子。在各种恶性肿瘤中,经常发现PTEN部分或完全失活。PI3K/AKT通路被认为是驱动细胞增殖的主要信号线索之一。因此,这条通路在高增殖性肿瘤中过度激活也许并不奇怪。重要的是,PI3K/AKT通路还协调上皮-间质转化(EMT),这对转移的起始至关重要,因此被视为转移性癌症治疗的一个有吸引力的靶点。研究表明,PTEN可抑制EMT,尽管这种作用的确切机制仍未完全阐明。本综述旨在系统整理已发表的关于PTEN在恶性肿瘤发生发展中作用的信息,主要关注其在EMT中对PI3K/AKT通路的调节。