Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of PKCζ-p53-p21 signaling pathway

Seung Hee Jung, Hyung Chul Lee, Hyun Jung Hwang, Hyun A. Park, Young Ah Moon, Bong Cho Kim, Hyeong Min Lee, Kwang Pyo Kim, Yong Nyun Kim, Byung Lan Lee, Jae Cheol Lee, Young-Gyu Ko, Heon Joo Park, Jae Seon Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the ACOT family that catalyzes hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. However, canonical and non-canonical functions of ACOT7 remain to be discovered. In this study, for the first time, ACOT7 was shown to be responsive to genotoxic stresses such as ionizing radiation (IR) and the anti-cancer drug doxorubicin in time- and dose-dependent manners. ACOT7 knockdown induced cytostasis via activation of the p53-p21 signaling pathway without a DNA damage response. PKCζ was specifically involved in ACOT7 depletion-mediated cell cycle arrest as an upstream molecule of the p53-p21 signaling pathway in MCF7 human breast carcinoma and A549 human lung carcinoma cells. Of the other members of the ACOT family, including ACOT1, 4, 8, 9, 11, 12, and 13 that were expressed in human, ACOT4, 8, and 12 were responsive to genotoxic stresses. However, none of those had a role in cytostasis via activation of the PKCζ-p53-p21 signaling pathway. Analysis of the ACOT7 prognostic value revealed that low ACOT7 levels prolonged overall survival periods in breast and lung cancer patients. Furthermore, ACOT7 mRNA levels were higher in lung cancer patient tissues compared to normal tissues. We also observed a synergistic effect of ACOT7 depletion in combination with either IR or doxorubicin on cell proliferation in breast and lung cancer cells. Together, our data suggest that a low level of ACOT7 may be involved, at least in part, in the prevention of human breast and lung cancer development via regulation of cell cycle progression.

Original languageEnglish
Pages (from-to)e2793
JournalCell death & disease
Volume8
Issue number5
DOIs
Publication statusPublished - 2017 May 18
Externally publishedYes

Fingerprint

Acyl Coenzyme A
Cell Cycle
Lung Neoplasms
Breast Neoplasms
DNA Damage
Ionizing Radiation
Doxorubicin
Coenzyme A
Cell Cycle Checkpoints
Nonesterified Fatty Acids
Protein Isoforms
Hydrolysis
Cell Proliferation
Carcinoma
Lung

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Jung, S. H., Lee, H. C., Hwang, H. J., Park, H. A., Moon, Y. A., Kim, B. C., ... Lee, J. S. (2017). Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of PKCζ-p53-p21 signaling pathway. Cell death & disease, 8(5), e2793. https://doi.org/10.1038/cddis.2017.202

Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of PKCζ-p53-p21 signaling pathway. / Jung, Seung Hee; Lee, Hyung Chul; Hwang, Hyun Jung; Park, Hyun A.; Moon, Young Ah; Kim, Bong Cho; Lee, Hyeong Min; Kim, Kwang Pyo; Kim, Yong Nyun; Lee, Byung Lan; Lee, Jae Cheol; Ko, Young-Gyu; Park, Heon Joo; Lee, Jae Seon.

In: Cell death & disease, Vol. 8, No. 5, 18.05.2017, p. e2793.

Research output: Contribution to journalArticle

Jung, SH, Lee, HC, Hwang, HJ, Park, HA, Moon, YA, Kim, BC, Lee, HM, Kim, KP, Kim, YN, Lee, BL, Lee, JC, Ko, Y-G, Park, HJ & Lee, JS 2017, 'Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of PKCζ-p53-p21 signaling pathway', Cell death & disease, vol. 8, no. 5, pp. e2793. https://doi.org/10.1038/cddis.2017.202
Jung, Seung Hee ; Lee, Hyung Chul ; Hwang, Hyun Jung ; Park, Hyun A. ; Moon, Young Ah ; Kim, Bong Cho ; Lee, Hyeong Min ; Kim, Kwang Pyo ; Kim, Yong Nyun ; Lee, Byung Lan ; Lee, Jae Cheol ; Ko, Young-Gyu ; Park, Heon Joo ; Lee, Jae Seon. / Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of PKCζ-p53-p21 signaling pathway. In: Cell death & disease. 2017 ; Vol. 8, No. 5. pp. e2793.
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abstract = "Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the ACOT family that catalyzes hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. However, canonical and non-canonical functions of ACOT7 remain to be discovered. In this study, for the first time, ACOT7 was shown to be responsive to genotoxic stresses such as ionizing radiation (IR) and the anti-cancer drug doxorubicin in time- and dose-dependent manners. ACOT7 knockdown induced cytostasis via activation of the p53-p21 signaling pathway without a DNA damage response. PKCζ was specifically involved in ACOT7 depletion-mediated cell cycle arrest as an upstream molecule of the p53-p21 signaling pathway in MCF7 human breast carcinoma and A549 human lung carcinoma cells. Of the other members of the ACOT family, including ACOT1, 4, 8, 9, 11, 12, and 13 that were expressed in human, ACOT4, 8, and 12 were responsive to genotoxic stresses. However, none of those had a role in cytostasis via activation of the PKCζ-p53-p21 signaling pathway. Analysis of the ACOT7 prognostic value revealed that low ACOT7 levels prolonged overall survival periods in breast and lung cancer patients. Furthermore, ACOT7 mRNA levels were higher in lung cancer patient tissues compared to normal tissues. We also observed a synergistic effect of ACOT7 depletion in combination with either IR or doxorubicin on cell proliferation in breast and lung cancer cells. Together, our data suggest that a low level of ACOT7 may be involved, at least in part, in the prevention of human breast and lung cancer development via regulation of cell cycle progression.",
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AU - Lee, Byung Lan

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