蛋白激酶AKT不同亚型影响乳腺癌恶性表型的研究进展

Advances in Understanding the Specific Roles Played by Different AKT Isoforms in Affecting Malignant Phenotypes of Breast Cancer

细胞的增殖、转移、存活等细胞生物学过程的异常对人类众多疾病尤其是恶性肿瘤的发生发展至关重要。大量研究表明,PI3K/AKT信号通路的异常激活在肿瘤的恶性转化过程中发挥重要作用并具有普遍意义。但是,目前的研究多集中于探讨AKT总的激酶活性,而往往忽视了AKT不同亚型的特异性功能。近年来在乳腺癌中的研究发现,AKT家族不同亚型的激酶分子在调控肿瘤细胞的存活、生长、增殖、代谢、转移等众多恶性表型方面发挥独特而关键的作用:与Akt1促进肿瘤细胞增殖、抑制肿瘤细胞转移的作用相反,Akt2在促进肿瘤细胞转移、抑制肿瘤细胞增殖方面发挥重要功能;此外,随着对AKT家族研究的深入,人们对Akt3的特异性生物学功能也有了新的认识。本文在此对AKT不同亚型与乳腺癌恶性表型之间关系的研究进展做一总结。

The abnormality of cell proliferation, migration and survival is pivotal in the pathogenesis of several human diseases especially cancer. Abnormal activation of PI3K/AKT pathway plays an essential role in the process of malignant transformation and has universal significance. Among numerous studies, the effect ofPI3K/AKT dysregnlation on the malignant phenotypes of breast cancer attracts more attention. Different isoforms of AKT play specific roles in regulating multiple malignant phenotypes such as cancer cell survival, growth, proliferation, metabolism, metastasis and so on. Overexpression of Aktl usually promotes cancer cell proliferation and inhibits tumor metastasis. However, contrary to the functions ofAkt1, overexpression of Akt2 often leads to enhanced tumor metastasis and sup- pressed cell proliferation. More recently, with the studies of AKT families going deeper, we now have a new understanding of the specific role of Akt3. Here, the relationships between different AKT isoforms and specific malignant phenotypes of breast cancer are summarizedand reviewed.