Islam Mohammad, Jones Sarah, Ellis Ian
Unit of Cell and Molecular Biology, School of Dentistry, University of Dundee, Park Place, Dundee DD1 4HR, UK.
Biomedicines. 2023 Nov 8;11(11):3001. doi: 10.3390/biomedicines11113001.
Metastasis is a critical step in the process of carcinogenesis and a vast majority of cancer-related mortalities result from metastatic disease that is resistant to current therapies. Cell migration and invasion are the first steps of the metastasis process, which mainly occurs by two important biological mechanisms, i.e., cytoskeletal remodelling and epithelial to mesenchymal transition (EMT). Akt (also known as protein kinase B) is a central signalling molecule of the PI3K-Akt signalling pathway. Aberrant activation of this pathway has been identified in a wide range of cancers. Several studies have revealed that Akt actively engages with the migratory process in motile cells, including metastatic cancer cells. The downstream signalling mechanism of Akt in cell migration depends upon the tumour type, sites, and intracellular localisation of activated Akt. In this review, we focus on the role of Akt in the regulation of two events that control cell migration and invasion in various cancers including head and neck squamous cell carcinoma (HNSCC) and the status of PI3K-Akt pathway inhibitors in clinical trials in metastatic cancers.
转移是致癌过程中的关键步骤，绝大多数与癌症相关的死亡是由对当前治疗有抗性的转移性疾病导致的。细胞迁移和侵袭是转移过程的第一步，主要通过两种重要的生物学机制发生，即细胞骨架重塑和上皮-间质转化（EMT）。Akt（也称为蛋白激酶B）是PI3K-Akt信号通路的核心信号分子。该通路的异常激活已在多种癌症中被发现。多项研究表明，Akt积极参与运动细胞（包括转移性癌细胞）的迁移过程。Akt在细胞迁移中的下游信号传导机制取决于肿瘤类型、部位以及活化Akt的细胞内定位。在本综述中，我们重点关注Akt在调控控制各种癌症（包括头颈部鳞状细胞癌，HNSCC）中细胞迁移和侵袭的两个事件中的作用，以及PI3K-Akt通路抑制剂在转移性癌症临床试验中的状况。
