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Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA
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Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA
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Journal Article
Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA
2018
Overview
People living with HIV/AIDS on antiretroviral therapy have increased risk of non-AIDS-defining cancers (NADCs). However, the underlying mechanism for development and progression of certain NADCs remains obscure. Here we show that exosomes released from HIV-infected T cells and those purified from blood of HIV-positive patients stimulate proliferation, migration and invasion of oral/oropharyngeal and lung cancer cells. The HIV transactivation response (TAR) element RNA in HIV-infected T-cell exosomes is responsible for promoting cancer cell proliferation and inducing expression of proto-oncogenes and Toll-like receptor 3 (TLR3)-inducible genes. These effects depend on the loop/bulge region of the molecule. HIV-infected T-cell exosomes rapidly enter recipient cells through epidermal growth factor receptor (EGFR) and stimulate ERK1/2 phosphorylation via the EGFR/TLR3 axis. Thus, our findings indicate that TAR RNA-containing exosomes from HIV-infected T cells promote growth and progression of particular NADCs through activation of the ERK cascade in an EGFR/TLR3-dependent manner.
HIV patients have an increased risk of developing non-AIDS-defining cancers but the molecular mechanisms underlying this predisposition are unclear. Here the authors show that exosomes secreted by HIV-infected T cells or isolated from the blood of HIV-positive patients, stimulate oncogenic properties of cancer cells through the activation of ERK1/2 signaling pathway.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/95
/ 14/19
/ 38
/ 631/67
/ 96/1
/ 96/34
/ Acquired immune deficiency syndrome
/ AIDS
/ Cancer
/ Epidermal growth factor receptors
/ Exosomes
/ HIV
/ Human immunodeficiency virus
/ Humanities and Social Sciences
/ RNA
/ Science
