PO.IM03.01 · 免疫学
HERV-K env基因通过多条信号通路（包括Ras/ERK信号通路和上皮-间质转化（EMT））促进乳腺癌细胞的致瘤性和转移
HERV-K env gene promotes tumorigenicity and metastasis through multiple signal pathways, including the Ras/ERK signaling pathway and epithelial-mesenchymal transition (EMT), in breast cancer cells
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：人内源性逆转录病毒K型（HERV-K）包膜（env）基因的过表达已在多种癌症中得到证实。然而，其作为"驱动因素"（启动肿瘤发生）还是"乘客因素"（仅仅是癌变状态的结果）的确切作用，在科学界仍是持续研究和争论的主题。
方法：通过稳定转染全长HERV-K env基因，在多种细胞系中研究了HERV-K表达的作用。
结果：在表达HERV-K env基因后，正常乳腺细胞中检测到K-Ras表达及其活性的增强。在表达HERV-K env的癌细胞中也观察到多种癌基因表达的增强。EMT标志物和beta-Catenin表达的上调伴随着HERV-K表达的上调。重要的是，在体内发现了向多个器官的转移。值得关注的是，用HERV-K表面蛋白（SU）免疫的小鼠所表现出的癌症预防效果优于用跨膜蛋白（TM）免疫者，这归因于CD8 T细胞的增加、Treg细胞的减少以及Th1细胞因子分泌的增加。
结论：HERV-K env基因是一种癌基因，通过上调Ras/Raf/MEK/ERK、EMT和PI3K/AKT通路的表达来促进肿瘤发生和转移。此外，HERV-K SU结构域（而非TM结构域）是一种能够触发免疫应答的肿瘤相关抗原（TAA）。
查看英文原文 English abstract
Background: Overexpression of the human endogenous retrovirus type K (HERV-K) envelope ( env ) gene was demonstrated in various cancers. However, its precise role as a "driver" (initiating tumor development) or "passenger" (simply a consequence of the cancerous state) is still a subject of ongoing research and debate within the scientific community.
Methods: The role(s) of HERV-K expression was investigated in multiple cell lines by stably transfecting with the full length HERV-K env gene.
Results: Enhanced expression of K-Ras and its activity were detected in normal breast cells after expressing the HERV-K env gene. Enhanced expression of multiple oncogenes was also observed in cancer cells that expressed HERV-K env . Upregulation of expression of EMT markers and beta-Catenin accompanied upregulation of HERV-K expression. Importantly, metastasis to multiple organs was discovered in vivo . Of interest, cancer prevention was demonstrated in mice immunized with HERV-K surface (SU) to a greater extent than with transmembrane protein (TM), due to increased CD8 T cells, decreased Treg cells, and increased Th1 cytokine secretion.
Conclusion: The HERV-K env gene is an oncogene that promotes tumorigenesis and metastasis through upregulated expression of the Ras/Raf/MEK/ERK, EMT, and PI3K/AKT pathways. In addition, the HERV-K SU domain but not the TM domain is a tumor-associated antigen (TAA) that can trigger immune responses.
利益披露 Disclosure
F. Wang-Johanning, None.