Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis

Yi Zhang, Yan Cheng, Xingcong Ren, Tsukasa Hori, Kathryn J. Huber-Keener, Li Zhang, Kai Lee Yap, David Liu, Lisa Shantz, Zheng Hong Qin, Suping Zhang, Jianrong Wang, Hong-Gang Wang, Ie Ming Shih, Jin-Ming Yang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, has emerging roles in cancer. We report here that NAC1 acts as a negative regulator of cellular senescence in transformed and nontransformed cells, and dysfunction of NAC1 induces senescence and inhibits its oncogenic potential.Weshow that NAC1 deficiency markedly activates senescence and inhibits proliferation in tumor cells treated with sublethal doses of γ-irradiation. In mouse embryonic fibroblasts from NAC1 knockout mice, following infection with a Ras virus, NAC1-/- cells undergo significantly more senescence and are either nontransformed or less transformed in vitro and less tumorigenic in vivo when compared with NAC1+/+ cells. Furthermore, we show that the NAC1-caused senescence blunting is mediated by ΔNp63, which exerts its effect on senescence through p21, and that NAC1 activates transcription of ΔNp63 under stressful conditions. Our results not only reveal a previously unrecognized function of NAC1, the molecular pathway involved and its impact on pathogenesis of tumor initiation and development, but also identify a novel senescence regulator that may be exploited as a potential target for cancer prevention and treatment.

Original languageEnglish (US)
Pages (from-to)4262-4275
Number of pages14
JournalCancer Research
Volume72
Issue number16
DOIs
StatePublished - Aug 15 2012

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Cell Aging
Nucleus Accumbens
Carcinogenesis
Cell Proliferation
Neoplasms
NFI Transcription Factors
Cell Nucleus
Knockout Mice
Fibroblasts
Viruses

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Zhang, Y., Cheng, Y., Ren, X., Hori, T., Huber-Keener, K. J., Zhang, L., ... Yang, J-M. (2012). Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis. Cancer Research, 72(16), 4262-4275. https://doi.org/10.1158/0008-5472.CAN-12-0139
Zhang, Yi ; Cheng, Yan ; Ren, Xingcong ; Hori, Tsukasa ; Huber-Keener, Kathryn J. ; Zhang, Li ; Yap, Kai Lee ; Liu, David ; Shantz, Lisa ; Qin, Zheng Hong ; Zhang, Suping ; Wang, Jianrong ; Wang, Hong-Gang ; Shih, Ie Ming ; Yang, Jin-Ming. / Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis. In: Cancer Research. 2012 ; Vol. 72, No. 16. pp. 4262-4275.
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abstract = "Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, has emerging roles in cancer. We report here that NAC1 acts as a negative regulator of cellular senescence in transformed and nontransformed cells, and dysfunction of NAC1 induces senescence and inhibits its oncogenic potential.Weshow that NAC1 deficiency markedly activates senescence and inhibits proliferation in tumor cells treated with sublethal doses of γ-irradiation. In mouse embryonic fibroblasts from NAC1 knockout mice, following infection with a Ras virus, NAC1-/- cells undergo significantly more senescence and are either nontransformed or less transformed in vitro and less tumorigenic in vivo when compared with NAC1+/+ cells. Furthermore, we show that the NAC1-caused senescence blunting is mediated by ΔNp63, which exerts its effect on senescence through p21, and that NAC1 activates transcription of ΔNp63 under stressful conditions. Our results not only reveal a previously unrecognized function of NAC1, the molecular pathway involved and its impact on pathogenesis of tumor initiation and development, but also identify a novel senescence regulator that may be exploited as a potential target for cancer prevention and treatment.",
author = "Yi Zhang and Yan Cheng and Xingcong Ren and Tsukasa Hori and Huber-Keener, {Kathryn J.} and Li Zhang and Yap, {Kai Lee} and David Liu and Lisa Shantz and Qin, {Zheng Hong} and Suping Zhang and Jianrong Wang and Hong-Gang Wang and Shih, {Ie Ming} and Jin-Ming Yang",
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Zhang, Y, Cheng, Y, Ren, X, Hori, T, Huber-Keener, KJ, Zhang, L, Yap, KL, Liu, D, Shantz, L, Qin, ZH, Zhang, S, Wang, J, Wang, H-G, Shih, IM & Yang, J-M 2012, 'Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis', Cancer Research, vol. 72, no. 16, pp. 4262-4275. https://doi.org/10.1158/0008-5472.CAN-12-0139

Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis. / Zhang, Yi; Cheng, Yan; Ren, Xingcong; Hori, Tsukasa; Huber-Keener, Kathryn J.; Zhang, Li; Yap, Kai Lee; Liu, David; Shantz, Lisa; Qin, Zheng Hong; Zhang, Suping; Wang, Jianrong; Wang, Hong-Gang; Shih, Ie Ming; Yang, Jin-Ming.

In: Cancer Research, Vol. 72, No. 16, 15.08.2012, p. 4262-4275.

Research output: Contribution to journalArticle

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T1 - Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis

AU - Zhang, Yi

AU - Cheng, Yan

AU - Ren, Xingcong

AU - Hori, Tsukasa

AU - Huber-Keener, Kathryn J.

AU - Zhang, Li

AU - Yap, Kai Lee

AU - Liu, David

AU - Shantz, Lisa

AU - Qin, Zheng Hong

AU - Zhang, Suping

AU - Wang, Jianrong

AU - Wang, Hong-Gang

AU - Shih, Ie Ming

AU - Yang, Jin-Ming

PY - 2012/8/15

Y1 - 2012/8/15

N2 - Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, has emerging roles in cancer. We report here that NAC1 acts as a negative regulator of cellular senescence in transformed and nontransformed cells, and dysfunction of NAC1 induces senescence and inhibits its oncogenic potential.Weshow that NAC1 deficiency markedly activates senescence and inhibits proliferation in tumor cells treated with sublethal doses of γ-irradiation. In mouse embryonic fibroblasts from NAC1 knockout mice, following infection with a Ras virus, NAC1-/- cells undergo significantly more senescence and are either nontransformed or less transformed in vitro and less tumorigenic in vivo when compared with NAC1+/+ cells. Furthermore, we show that the NAC1-caused senescence blunting is mediated by ΔNp63, which exerts its effect on senescence through p21, and that NAC1 activates transcription of ΔNp63 under stressful conditions. Our results not only reveal a previously unrecognized function of NAC1, the molecular pathway involved and its impact on pathogenesis of tumor initiation and development, but also identify a novel senescence regulator that may be exploited as a potential target for cancer prevention and treatment.

AB - Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, has emerging roles in cancer. We report here that NAC1 acts as a negative regulator of cellular senescence in transformed and nontransformed cells, and dysfunction of NAC1 induces senescence and inhibits its oncogenic potential.Weshow that NAC1 deficiency markedly activates senescence and inhibits proliferation in tumor cells treated with sublethal doses of γ-irradiation. In mouse embryonic fibroblasts from NAC1 knockout mice, following infection with a Ras virus, NAC1-/- cells undergo significantly more senescence and are either nontransformed or less transformed in vitro and less tumorigenic in vivo when compared with NAC1+/+ cells. Furthermore, we show that the NAC1-caused senescence blunting is mediated by ΔNp63, which exerts its effect on senescence through p21, and that NAC1 activates transcription of ΔNp63 under stressful conditions. Our results not only reveal a previously unrecognized function of NAC1, the molecular pathway involved and its impact on pathogenesis of tumor initiation and development, but also identify a novel senescence regulator that may be exploited as a potential target for cancer prevention and treatment.

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