CXCR7 is inducible by HTLV‐1 Tax and promotes growth and survival of HTLV‐1‐infected T cells

• Published in: International journal of cancer 2009-11, Vol.125 (9), p.2229-2235
• Main Authors: Jin, Zhe, Nagakubo, Daisuke, Shirakawa, Aiko‐Konno, Nakayama, Takashi, Shigeta, Akiko, Hieshima, Kunio, Yamada, Yasuaki, Yoshie, Osamu
• Format: Article
• Language: English
• Subjects: cell growth; Cell Line; Cell Proliferation; Cell Survival; CXCR7; Gene Products, tax - physiology; HTLV‐1; Human T-lymphotropic virus; Human T-lymphotropic virus 1; Humans; NF-kappa B - metabolism; NF‐kB; Receptors, CXCR - genetics; RNA, Messenger - analysis; T-Lymphocytes - physiology; T-Lymphocytes - virology; Tax
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.24612

Human T‐lymphotropic virus type 1 (HTLV‐1), the etiological agent of adult T‐cell leukemia (ATL), encodes the potent transcriptional activator Tax, which is required for HTLV‐1‐induced immortalization of T cells. CXCR7 is an atypical chemokine receptor frequently expressed by tumor cells and known to promote cell growth and survival. We found that HTLV‐1‐immortalized T cells expressing Tax consistently expressed CXCR7. Induction of Tax in JPX‐9 upregulated CXCR7. Wild‐type Tax efficiently activated the CXCR7 promoter via a proximal NF‐κB site, while a mutant Tax selectively defective in NF‐κB activation did not. CCX754, a synthetic CXCR7 antagonist, inhibited cell growth and increased apoptosis of HTLV‐1‐immortalized T cells. Knockdown of CXCR7 by small interfering RNA also reduced cell growth. Stable expression of CXCR7 in a CXCR7‐negative ATL cell line promoted cell growth and survival. Taken together, CXCR7 is inducible by Tax and may play an important role in HTLV‐1‐induced immortalization of T cells by promoting growth and survival of HTLV‐1‐infected T cells. © 2009 UICC