title: CXCR7 is inducible by HTLV-1 Tax and promotes growth and survival of HTLV-1-infected T cells.
abstract: 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-kappaB site, while a mutant Tax selectively defective in NF-kappaB 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.
authors.affiliation: Department of Microbiology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jin
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nagakubo
authors.forename: Aiko-Konno
authors.initials: AK
authors.lastname: Shirakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
authors.forename: Akiko
authors.initials: A
authors.lastname: Shigeta
authors.forename: Kunio
authors.initials: K
authors.lastname: Hieshima
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D016356:Gene Products, tax / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D054387:Receptors, CXCR / Q000235:genetics*; D013601:T-Lymphocytes / Q000502:physiology* / Q000821:virology*
chemical_list: C501896:ACKR3 protein, human; D016356:Gene Products, tax; D016328:NF-kappa B; D012333:RNA, Messenger; D054387:Receptors, CXCR; C514970:tax protein, Human T-lymphotrophic virus 1