Novosibirsk State University, Novosibirsk, 630090, Russia.
Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, 630117, Russia.
Biochemistry (Mosc). 2022 Nov;87(11):1310-1326. doi: 10.1134/S0006297922110104.
Tumor-suppressive effects of PTEN are well-known, but modern evidence suggest that they are not limited to its ability to inhibit pro-oncogenic PI3K/AKT signaling pathway. Features of PTEN structure facilitate its interaction with substrates of different nature and display its activity in various ways both in the cytoplasm and in cell nuclei, which makes it possible to take a broader look at its ability to suppress tumor growth. The possible mechanisms of the loss of PTEN effects are also diverse - PTEN can be regulated at many levels, leading to change in the protein activity or its amount in the cell, while their significance for the development of malignant tumors has yet to be studied. Here we summarize the current data on the PTEN structure, its functions and changes in its regulatory mechanisms during malignant transformation of the cells, focusing on one of the most sensitive to the loss of PTEN types of malignant tumors - endometrial cancer.
PTEN 的抑瘤作用早已众所周知,但现代证据表明,其作用不仅局限于抑制致癌性的 PI3K/AKT 信号通路。PTEN 结构的特点使其能够与不同性质的底物相互作用,并在细胞质和细胞核中以各种方式发挥其活性,这使得人们可以更全面地观察其抑制肿瘤生长的能力。PTEN 作用丧失的可能机制也多种多样——PTEN 可以在多个水平上受到调节,导致蛋白活性或其在细胞内的含量发生变化,而其对恶性肿瘤发展的意义仍有待研究。在这里,我们总结了目前关于 PTEN 结构、功能及其在细胞恶性转化过程中调节机制变化的相关数据,重点关注对 PTEN 缺失最敏感的一种恶性肿瘤——子宫内膜癌。