Title:The Role of LMP1 in Epstein-Barr Virus-associated Gastric Cancer
Volume: 24
Issue: 2
关键词:
潜伏膜蛋白1 (LMP1), Eb病毒相关胃癌(EBVaGC),细胞凋亡,信号通路,甲基化,肿瘤微环境。
摘要: EBV promotes many cancers such as lymphoma, nasopharyngeal carcinoma, and gastric;
Latent Membrane Protein 1 (LMP1) is considered to be a major oncogenic protein encoded by Epstein–
Barr virus (EBV). LMP1 functions as a carcinogen in lymphoma and nasopharyngeal carcinoma,
and LMP1 may also promote gastric cancer. The expression level of LMP1 in host cells is a key
determinant in tumorigenesis and maintenance of virus specificity. By promoting cell immortalization
and cell transformation, promoting cell proliferation, affecting immunity, and regulating cell apoptosis,
LMP1 plays a crucial tumorigenic role in epithelial cancers. However, very little is currently
known about LMP1 in Epstein-Barr virus-associated gastric cancer (EBVaGC); the main reason is
that the expression level of LMP1 in EBVaGC is comparatively lower than other EBV-encoded proteins,
such as The Latent Membrane Protein 2A (LMP2A), Epstein-Barr nuclear antigen 1 (EBNA1)
and BamHI-A rightward frame 1 (BARF1), to date, there are few studies related to LMP1 in EBVaGC.
Recent studies have demonstrated that LMP1 promotes EBVaGC by affecting The phosphatidylinositol
3-kinase- Akt (PI3K-Akt), Nuclear factor-kappa B (NF-κB), and other signaling pathways
to regulate many downstream targets such as Forkhead box class O (FOXO), C-X-C-motif chemokine
receptor (CXCR), COX-2 (Cyclooxygenase-2); moreover, the gene methylation induced by LMP1 in
EBVaGC has become one of the characteristics that distinguish this gastric cancer (GC) from other
types of gastric cancer and LMP1 also promotes the formation of the tumor microenvironment (TME)
of EBVaGC in several ways. This review synthesizes previous relevant literature, aiming to highlight
the latest findings on the mechanism of action of LMP1 in EBVaGC, summarize the function of
LMP1 in EBVaGC, lay the theoretical foundation for subsequent new research on LMP1 in EBVaGC,
and contribute to the development of novel LMP1-targeted drugs.