TY - JOUR
T1 - Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of PKCζ-p53-p21 signaling pathway
AU - Jung, Seung Hee
AU - Lee, Hyung Chul
AU - Hwang, Hyun Jung
AU - Park, Hyun A.
AU - Moon, Young Ah
AU - Kim, Bong Cho
AU - Lee, Hyeong Min
AU - Kim, Kwang Pyo
AU - Kim, Yong Nyun
AU - Lee, Byung Lan
AU - Lee, Jae Cheol
AU - Ko, Young Gyu
AU - Park, Heon Joo
AU - Lee, Jae Seon
N1 - Copyright:
This record is sourced from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
PY - 2017/5/18
Y1 - 2017/5/18
N2 - 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.
AB - 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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U2 - 10.1038/cddis.2017.202
DO - 10.1038/cddis.2017.202
M3 - Article
C2 - 28518146
AN - SCOPUS:85042660888
VL - 8
SP - e2793
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 5
ER -
