AKT2

Detailed Information

Recent Research Progress

AKT, also known as protein kinase B (PKB), is a serine/threonine protein kinase. It can be activated by extracellular stimuli and regulate cell proliferation and survival by regulating cell signaling pathways. AKT is a central link in the PI3K/AKT signal transduction pathway and is mainly responsible for PI3K-initiated biological information transduction. AKT is a central link in the PI3K/AKT signal transduction pathway and is mainly responsible for PI3K-initiated biological information transduction. Its functions include cell cycle regulation and apoptosis initiation, involvement in tumor angiogenesis and lymphangiogenesis, cell invasiveness, and other pathological processes of malignant tumors. AKT in human cells can be divided into three subtypes: Akt1, Akt2, and Akt3. Akt2 is located on 19q13.2 of the human chromosome and contains 22 exons. It is an important factor in PI3K/AKT signaling pathway and can regulate cell proliferation, differentiation and survival in physiological and pathological processes. A large number of experiments have shown that Akt2 is closely related to the proliferation and metastasis of tumor cells. Overexpression of Akt2 protein exists in many tumor tissues.

Figure 1. Dysregulation of the PI3K/AKT signaling pathway promotes AKT hyperactivation and tumorigenesis. (Rodgers, et al. 2017).

Akt2 and Tumor

The occurrence and development of malignant tumors are regulated by the instability of genes and the microenvironment of the tumor. In the process of tumorigenesis, development, and prolongation, there are genes and different signal pathways that are matched to the tumors. P13K/AKT signaling pathways are involved in the regulation of various cells in various signaling pathways. Overactivation of this pathway plays a key role in the development of human malignancies and cancer, and AKT2 is closely related to the invasion and metastasis of malignant tumors as an important regulatory factor.

Akt2 and Ovarian Cancer

The PI3K/AKT signaling pathway is involved in the adhesion and invasion ability of tumors. In particular, Akt2 activation plays an important role in the development of ovarian cancer. Khabele et al. showed that AKT2-dependent signaling plays an important role in the survival of some EGFR-expressing ovarian cancer cells such as OVCAR-3 cells, so it can be used as a new method for the treatment of EGFR-expressing nest cells in the future. Teng et al. found that negative regulation of microRNA-29B (miR-29b) can cause downregulation of HK2/PKM2 expression. Thus reducing the Warburg effect and slowing the progression of ovarian cancer, while the overexpression of miR-29b can negatively affect the glucose metabolism of tumor cells, further confirming that miR-29b regulates the Warburg effect of epithelial ovarian cancer through AKT2/AKT3. AKT2 and AKT3 may promote the development of ovarian cancer cells by enhancing the glycolytic metabolism of cancer cells.

Akt2 and Breast Cancer

Breast cancer (BC) is the most common type of cancer in women. Its mortality is mainly due to distant metastasis. Studies confirm that P13K is the most active signaling pathway in 70% of invasive breast cancer patients. Mutlu et al. observed the proliferation and invasion of breast cancer cells by a microRNA simultaneously acting on the P13K and MAPK signaling pathways, finding that miR-564 can directly target these signals, including the AKT2 gene network as a potential tumor suppressor.

Akt2 and Malignant Glioma

Malignant glioma is a type of tumor with a very high degree of malignancy. Its invasion to the surrounding brain tissue is the main cause to death. Studies have shown that the expression level of Akt2 protein in gliomas can increase with the degree of malignancy of the tumor. The mechanism may be that the PI3K/AKT signaling pathway mainly plays a regulatory role at the protein level, and the increased expression is mainly due to the level regulation of translation or post-translation rather than the level up-regulation of gene transcription. Emdad et al. found that AEG-I-AKT2 interaction regulation can promote the phosphorylation of the apoptosis-related protein Bcl-2 associated death promoter. This indicates that AEG-I-AKT2 plays a complex protective role in the mitochondrial apoptotic pathway of glioma, confirming that AKT2 is closely related to the survival, proliferation and invasion of glioma cells.

Akt2 and Pancreatic Cancer

Abnormal activation of P13K signal can increase the proliferation, invasion and migration of pancreatic cancer cells. Phosphatase and tensin (PTEN) homologues have been shown to antagonize the P13K signaling pathway and act as inhibitors of the P13K signaling pathway. It has been confirmed that Akt2 is an important regulator of P13K signaling pathway. It is an oncogene that is abnormally expressed and activated in pancreatic cancer, so it is closely related to the malignant phenotype of pancreatic cancer. Sun et al. found that the expression of miR-615-5p in PDAC tissues was significantly lower than that in paracancerous normal tissues, further confirming that miR-615-5p can partially inhibit AKT2 to exert its ability to inhibit tumor growth, invasion, and migration. This finding reveals that miR-615-5p can act as a tumor suppressor of PDAC.

Akt2 and Non-small Cell Lung Cancer

AKT plays a key role in the over-activated expression of lung cancer cells in NSCLC. Wang et al. applied immunohistochemistry to detect the expression of Akt2, Cyclin D1, and MMP-9 in non-small cell lung cancer (NSCLC). The results showed that the positive rate of Akt2 in NSCLC was significantly higher than that in paracancerous and non-neoplastic lung tissues, and the expression of Akt2 is closely related to Cyclin D1 and MMP-9.The mechanism is that MMP-9 can degrade and destroy the main components of type IV and V collagen and gelatin in extracellular matrix and basement membrane, enhance the invasion ability of cancer cells to surrounding normal tissues, and lead to the proliferation and metastasis of tumors.

Akt2 and Liver Cancer

Studies have confirmed that P13K/AKT signaling pathway plays an important role in the formation and development of liver tumors, and it is also a popular target pathway for anti-liver cancer targeted drug therapy in recent years. Wang et al. have confirmed that miR-302b blocks the progression of liver cancer through the AKT2 signaling pathway, especially for the fine growth cycle of liver cancer, and thus can inhibit the growth of liver tumors.Liu et al. studied on the miRNA level and also found that miRNA-137 directly induces AKT2 signaling pathway and inhibits the growth and metastasis of hepatocellular carcinoma cells after being induced by transcription factor FoxD3.The proposed FoxD3/miR-137/AKT2 signaling axis has also become a new target for liver cancer treatment.

Akt2 plays an important role in the proliferation, differentiation, apoptosis and invasion and metastasis of various malignant tumor cells such as breast cancer, ovarian cancer and pancreatic cancer. With the deep research on the structure and function of Akt2, it has been found that it is related to the expression of proteins on various cell pathways and forms a complex regulatory network. In the future, the focus of the study will be on the regulatory mechanisms of AKT2 and the regulatory proteins of various cellular pathways. Then, an anticancer drug targeting Akt2 will be developed.