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HIV-1 Tat Promotes Kaposi's Sarcoma-Associated Herpesvirus (KSHV) vIL-6-Induced Angiogenesis and Tumorigenesis by Regulating PI3K/PTEN/AKT/GSK-3β Signaling Pathway

Zhou, F and Xue, M and Qin, D and Zhu, X and Wang, C and Zhu, J and Hao, T and Cheng, L and Chen, X and Bai, Z and Feng, N and Gao, SJ and Lu, C (2013) HIV-1 Tat Promotes Kaposi's Sarcoma-Associated Herpesvirus (KSHV) vIL-6-Induced Angiogenesis and Tumorigenesis by Regulating PI3K/PTEN/AKT/GSK-3β Signaling Pathway. PLoS ONE, 8 (1).

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Abstract

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is etiologically associated with KS, the most common AIDS-related malignancy. KS is characterized by vast angiogenesis and hyperproliferative spindle cells. We have previously reported that HIV-1 Tat can trigger KSHV reactivation and accelerate Kaposin A-induced tumorigenesis. Here, we explored Tat promotion of KSHV vIL-6-induced angiogenesis and tumorigenesis. Tat promotes vIL-6-induced cell proliferation, cellular transformation, vascular tube formation and VEGF production in culture. Tat enhances vIL-6-induced angiogenesis and tumorigenesis of fibroblasts and human endothelial cells in a chicken chorioallantoic membrane (CAM) model. In an allograft model, Tat promotes vIL-6-induced tumorigenesis and expression of CD31, CD34, SMA, VEGF, b-FGF, and cyclin D1. Mechanistic studies indicated Tat activates PI3K and AKT, and inactivates PTEN and GSK-3β in vIL-6 expressing cells. LY294002, a specific inhibitor of PI3K, effectively impaired Tat's promotion of vIL-6-induced tumorigenesis. Together, these results provide the first evidence that Tat might contribute to KS pathogenesis by synergizing with vIL-6, and identify PI3K/AKT pathway as a potential therapeutic target in AIDS-related KS patients. © 2013 Zhou et al.


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Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Zhou, F
Xue, M
Qin, D
Zhu, X
Wang, C
Zhu, J
Hao, T
Cheng, L
Chen, X
Bai, Z
Feng, N
Gao, SJ
Lu, C
Centers: Other Centers, Institutes, or Units > Hillman Cancer Center
Date: 2 January 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 1
DOI or Unique Handle: 10.1371/journal.pone.0053145
Refereed: Yes
PubMed Central ID: PMC3534639
PubMed ID: 23301033
Date Deposited: 14 Mar 2013 14:13
Last Modified: 05 Feb 2019 16:55
URI: http://d-scholarship.pitt.edu/id/eprint/17712

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