Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

Jiang, Ningni; Dai, Qijie; Su, Xiaorui; Fu, Jianjiang; Feng, Xuancheng; Peng, Juan

doi:10.1007/s11033-020-05435-1

Cited by 355 publications

(252 citation statements)

References 406 publications

(343 reference statements)

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“…Previous research shown that focal adhesion kinase was a crucial signaling molecule in regulating fibrotic and immunosuppressive TME and its expression was negatively associated with the infiltration of T cells (33). PI3K-Akt signaling pathway is a well-known transduction pathway involved in tumorigenesis, proliferation, and immune microenvironment (34). In this study, KEGG pathway analysis showed that enrichments of the immune-related DEGs clustered observably in focal adhesion and PI3K-Akt signaling pathway.…”

Section: Discussionmentioning

confidence: 48%

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

Teng

Liu

et al. 2020

Front. Oncol.

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The tumor microenvironment (TME) is a complex system that plays an important role in tumor development and progression, but the current knowledge about its effect on bladder cancer (BC) is scarce. In this study, we performed a comprehensive analysis of the relationship between the TME and gene expression profiles to identify prognostic biomarkers for BC. The ESTIMATE algorithm was used to calculate immune and stromal scores of BC patients who were obtained from the Gene Expression Omnibus database. We found that the immune and stromal scores were associated with clinical characteristics and the prognosis of BC patients. Based on these scores, 104 immune-related differentially expressed genes were identified. Further, functional enrichment analysis revealed that these genes were mainly involved in the immune-related biological processes and signaling pathways. Three prognostic genes were then identified and used to establish a risk prediction model using Cox regression analyses. Kaplan-Meier survival analysis showed that the expression levels of COL1A1, COMP, and SERPINE2 significantly correlated with cancer-specific survival and overall survival of BC patients. Additionally, we validated the prognostic values of these genes using two independent cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases. Finally, the relationships between the three prognostic genes and several immune cells were evaluated using Tumor Immune Estimation Resource, indicating that the expression levels of COL1A1, COMP, and SERPINE2 correlated positively with the tumor infiltration levels of CD4 + T cells and macrophages. In conclusion, the current study comprehensively analyzed the TME and presented immune-related prognostic genes for BC, providing new insights into immunotherapeutic strategies for BC patients.

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Section: Discussionmentioning

confidence: 48%

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

Teng

Liu

et al. 2020

Front. Oncol.

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“…Akt is a serine-threonine kinase partially activated through the phosphorylation of Thr-308 and fully activated upon Ser-473 phosphorylation 13 . Notably, Akt is constitutively activated in up to 70% of human melanomas and plays an important role in melanoma pathogenesis 14 .…”

Section: Introductionmentioning

confidence: 99%

A20 promotes melanoma progression via the activation of Akt pathway

Wang

Guo

et al. 2020

Cell Death Dis

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Melanoma is the most life-threatening skin cancer with increasing incidence around the world. Although recent advances in targeted therapy and immunotherapy have brought revolutionary progress of the treatment outcome, the survival of patients with advanced melanoma remains unoptimistic, and metastatic melanoma is still an incurable disease. Therefore, to further understand the mechanism underlying melanoma pathogenesis could be helpful for developing novel therapeutic strategy. A20 is a crucial ubiquitin-editing enzyme implicated immunity regulation, inflammatory responses and cancer pathogenesis. Herein, we report that A20 played an oncogenic role in melanoma. We first found that the expression of A20 was significantly up-regulated in melanoma cell lines. Then, we showed that knockdown of A20 suppressed melanoma cell proliferation in vitro and melanoma growth in vivo through the regulation of cell-cycle progression. Moreover, A20 could potentiate the invasive and migratory capacities of melanoma cell in vitro and melanoma metastasis in vivo by promoting epithelial–mesenchymal transition (EMT). Mechanistically, we found that Akt activation mediated the oncogenic effect of A20 on melanoma development, with the involvement of glycolysis. What’s more, the up-regulation of A20 conferred the acquired resistance to Vemurafenib in BRAF-mutant melanoma. Taken together, we demonstrated that up-regulated A20 promoted melanoma progression via the activation of Akt pathway, and that A20 could be exploited as a potential therapeutic target for melanoma treatment.

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“…Wnt/β-catenin is one of the main signalin mesenchymal transition (EMT) and plays a key role in metasta pathway inhibited the development of metastases in GC mode PI3K/AKT/mTOR is involved in the regulation of the cell c and metabolism. In a tumor cell, PI3K/AKT/mTOR is one of regulation of proliferation, invasion, and migration [9]. Protei proteins of the PI3K/AKT/mTOR pathway.…”

Section: Introductionmentioning

confidence: 99%

“…Suppression of the Wnt/β-catenin development of metastases in GC models [7,8]. is involved in the regulation of the cell cycle and processes such as cell growth tumor cell, PI3K/AKT/mTOR is one of the main signaling pathways in the ion, invasion, and migration [9]. Protein kinase B (AKT) is one of the central KT/mTOR pathway.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers

et al. 2020

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Gastric cancer (GC) is one of the most common and difficult diseases to treat. The study of signaling pathway regulation by microRNA provides information on the mechanisms of GC development and is the basis for biomarker creation. In this study, a circuit of microRNA interactions with signaling pathways was constructed. The microRNAs, associated with metastasis and chemoresistance, are described. In most cases, microRNAs in GC regulate the Wnt/β-catenin, PI3K/AKT/mTOR, RAS/RAF/ERK/MAPK, NF-kB, TGF-β, and JAK/STAT pathways. Part of the microRNA acts on several target genes that function in different pathways. This often leads to an intensification of the induced processes. MicroRNAs have also been described that have the opposite effect on different pathways, causing different functional consequences. By acting on several target genes, or genes associated with several pathways, microRNAs can function in a signaling network. MicroRNAs associated with metastasis most often interact with the Wnt/β-catenin pathway. MicroRNAs affecting chemoresistance, in most cases, affect the regulators of apoptosis and are associated with the PI3K/AKT/mTOR pathway. The characteristics of microRNAs proposed as candidates for GC biomarkers were analyzed. The currently developed diagnostic and prognostic panels of microRNAs are also considered.

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Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

Cited by 355 publications

References 406 publications

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

A20 promotes melanoma progression via the activation of Akt pathway

MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers

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