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).
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
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| 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, Offices, 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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