E2F2 inhibition induces autophagy via the PI3K/Akt/mTOR pathway in gastric cancer
Autor: | Liwei Shen, Jing Lv, Hui Li, Gongjun Wang, Shufen Zhao, Wensheng Qiu, Peige Wang, Yingji Ma, Shihai Liu, Zhiwei Liang |
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Rok vydání: | 2020 |
Předmět: |
Male
Aging autophagy Programmed Cell Death 1 Receptor Biology B7-H1 Antigen Metastasis E2F2 Transcription Factor Cell Movement Stomach Neoplasms Cell Line Tumor medicine Biomarkers Tumor Humans metastasis Neoplasm Invasiveness Protein Interaction Maps RNA Messenger Protein kinase B PI3K/AKT/mTOR pathway E2F2 Aged Genome Human TOR Serine-Threonine Kinases gastric cancer Autophagy Cancer Cell migration Cell Biology DNA Methylation medicine.disease Prognosis PI3K/Akt/mTOR pathway Up-Regulation Gene Expression Regulation Neoplastic Multivariate Analysis Cancer research Immunohistochemistry Female Phosphatidylinositol 3-Kinase Proto-Oncogene Proteins c-akt Signal Transduction Research Paper |
Zdroj: | Aging (Albany NY) |
ISSN: | 1945-4589 |
Popis: | Background E2F2 is a member of the E2F transcription factor family and has important but not fully understood biological functions in cancers. The biological role of E2F2 in gastric cancer (GC) also remains unclear. Methods We examined the expression levels of E2F2 in GC using publicly available datasets such as TIMER, Oncomine, GEPIA, UALCAN, etc., and in our patient cohort, using quantitative real-time PCR, western blotting, and immunohistochemistry. We further investigated the effects of E2F2 on phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling, autophagy, and the migration and invasion of GC cells by the wound healing assay, Transwell assay and transmission electron microscopy. Results E2F2 was highly expressed in both GC tissues and cells compared with normal gastric tissues/cells. High E2F2 expression was associated with poor overall survival (OS). In addition, the expression of E2F2 in GC was strongly correlated with a variety of immune markers. E2F2 overexpression promoted the migration and invasiveness of GC cells in vitro through inhibition of PI3K/Akt/mTOR-mediated autophagy. Conclusion High E2F2 expression was associated with the characteristics of invasive tumors and poor prognosis. E2F2 also had potential modulatory effects on tumor immunity. We discovered a novel function of E2F2 in the regulation of PI3K/Akt/mTOR-mediated autophagy and the downstream processes of cell migration and invasion. |
Databáze: | OpenAIRE |
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