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Oncogenic Herpesvirus KSHV Hijacks BMP-Smad1-Id Signaling to Promote Tumorigenesis | |
2014 | |
发表期刊 | PLOS PATHOGENS |
ISSN | 1553-7366 |
EISSN | 1553-7374 |
卷号 | 10期号:7 |
发表状态 | 已发表 |
DOI | 10.1371/journal.ppat.1004253 |
摘要 | Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), a malignancy commonly found in AIDS patients. Whether KS is a true neoplasm or hyperplasia has been a subject of intensive debate until recently when KSHV is unequivocally shown to efficiently infect, immortalize and transform rat primary mesenchymal precursor cells (MM). Moreover, KSHV-transformed MM cells (KMM) efficiently induce tumors with hallmark features of KS when inoculated into nude mice. Here, we showed Smad1 as a novel binding protein of KSHV latency-associated nuclear antigen (LANA). LANA interacted with and sustained BMP-activated p-Smad1 in the nucleus and enhanced its loading on the Id promoters. As a result, Ids were significantly up-regulated in KMM cells and abundantly expressed in human KS lesions. Strikingly, genetic and chemical inhibition of the BMP-Smad1-Id pathway blocked the oncogenic phenotype of KSHV-transformed cells in vitro and in vivo. These findings illustrate a novel mechanism by which a tumor virus hijacks and converts a developmental pathway into an indispensable oncogenic pathway for tumorigenesis. Importantly, our results demonstrate the efficacy of targeting the BMP-Smad1-Id pathway for inhibiting the growth of KSHV-induced tumors, and therefore identify the BMP pathway as a promising therapeutic target for KS. |
URL | 查看原文 |
WOS研究方向 | Microbiology ; Parasitology ; Virology |
WOS类目 | Microbiology ; Parasitology ; Virology |
WOS记录号 | WOS:000340551000039 |
WOS关键词 | EPSTEIN-BARR-VIRUS ; BONE MORPHOGENETIC PROTEINS ; KAPOSIS-SARCOMA ; NUCLEAR ANTIGEN ; ID PROTEINS ; TGF-BETA ; LATENT MEMBRANE-PROTEIN-1 ; CELLULAR-TRANSFORMATION ; EXPRESSION ; GROWTH |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120797 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Gao, Shou-Jiang; Lan, Ke |
作者单位 | 1.Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China 2.Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA |
推荐引用方式 GB/T 7714 | Liang, Deguang,Hu, Hao,Li, Shasha,et al. Oncogenic Herpesvirus KSHV Hijacks BMP-Smad1-Id Signaling to Promote Tumorigenesis[J]. PLOS PATHOGENS,2014,10(7). |
APA | Liang, Deguang.,Hu, Hao.,Li, Shasha.,Dong, Jiazhen.,Wang, Xing.,...&Lan, Ke.(2014).Oncogenic Herpesvirus KSHV Hijacks BMP-Smad1-Id Signaling to Promote Tumorigenesis.PLOS PATHOGENS,10(7). |
MLA | Liang, Deguang,et al."Oncogenic Herpesvirus KSHV Hijacks BMP-Smad1-Id Signaling to Promote Tumorigenesis".PLOS PATHOGENS 10.7(2014). |
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