Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis.

DNA damage triggers a network of signaling events that leads to cell cycle arrest or apoptosis. This DNA damage response acts as a mechanism to prevent cancer development. It has been reported that fatty acids (FAs) synthesis is increased in many human tumors while inhibition of fatty acid synthase...

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Autores principales:	Li Zeng, Guang-Zhi Wu, Kim Jee Goh, Yew Mun Lee, Chuo Chung Ng, Ang Ben You, Jianhe Wang, Deyong Jia, Aijun Hao, Qiang Yu, Baojie Li
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f61b9e16b56d43aba5b5ddd2df35e5b1
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spelling	oai:doaj.org-article:f61b9e16b56d43aba5b5ddd2df35e5b12021-11-25T06:12:09ZSaturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis.1932-620310.1371/journal.pone.0002329https://doaj.org/article/f61b9e16b56d43aba5b5ddd2df35e5b12008-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18523653/?tool=EBIhttps://doaj.org/toc/1932-6203DNA damage triggers a network of signaling events that leads to cell cycle arrest or apoptosis. This DNA damage response acts as a mechanism to prevent cancer development. It has been reported that fatty acids (FAs) synthesis is increased in many human tumors while inhibition of fatty acid synthase (FASN) could suppress tumor growth. Here we report that saturated fatty acids (SFAs) play a negative role in DNA damage response. Palmitic acid, as well as stearic acid and myristic acid, compromised the induction of p21 and Bax expression in response to double stranded breaks and ssDNA, while inhibition or knockdown of FASN enhanced these cellular events. SFAs appeared to regulate p21 and Bax expression via Atr-p53 dependent and independent pathways. These effects were only observed in primary mouse embryonic fibroblasts and osteoblasts, but not in immortalized murine NIH3T3, or transformed HCT116 and MCF-7 cell lines. Accordingly, SFAs showed some positive effects on proliferation of MEFs in response to DNA damage. These results suggest that SFAs, by negatively regulating the DNA damage response pathway, might promote cell transformation, and that increased synthesis of SFAs in precancer/cancer cells might contribute to tumor progression and drug resistance.Li ZengGuang-Zhi WuKim Jee GohYew Mun LeeChuo Chung NgAng Ben YouJianhe WangDeyong JiaAijun HaoQiang YuBaojie LiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 6, p e2329 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Li Zeng Guang-Zhi Wu Kim Jee Goh Yew Mun Lee Chuo Chung Ng Ang Ben You Jianhe Wang Deyong Jia Aijun Hao Qiang Yu Baojie Li Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis.
description	DNA damage triggers a network of signaling events that leads to cell cycle arrest or apoptosis. This DNA damage response acts as a mechanism to prevent cancer development. It has been reported that fatty acids (FAs) synthesis is increased in many human tumors while inhibition of fatty acid synthase (FASN) could suppress tumor growth. Here we report that saturated fatty acids (SFAs) play a negative role in DNA damage response. Palmitic acid, as well as stearic acid and myristic acid, compromised the induction of p21 and Bax expression in response to double stranded breaks and ssDNA, while inhibition or knockdown of FASN enhanced these cellular events. SFAs appeared to regulate p21 and Bax expression via Atr-p53 dependent and independent pathways. These effects were only observed in primary mouse embryonic fibroblasts and osteoblasts, but not in immortalized murine NIH3T3, or transformed HCT116 and MCF-7 cell lines. Accordingly, SFAs showed some positive effects on proliferation of MEFs in response to DNA damage. These results suggest that SFAs, by negatively regulating the DNA damage response pathway, might promote cell transformation, and that increased synthesis of SFAs in precancer/cancer cells might contribute to tumor progression and drug resistance.
format	article
author	Li Zeng Guang-Zhi Wu Kim Jee Goh Yew Mun Lee Chuo Chung Ng Ang Ben You Jianhe Wang Deyong Jia Aijun Hao Qiang Yu Baojie Li
author_facet	Li Zeng Guang-Zhi Wu Kim Jee Goh Yew Mun Lee Chuo Chung Ng Ang Ben You Jianhe Wang Deyong Jia Aijun Hao Qiang Yu Baojie Li
author_sort	Li Zeng
title	Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis.
title_short	Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis.
title_full	Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis.
title_fullStr	Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis.
title_full_unstemmed	Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis.
title_sort	saturated fatty acids modulate cell response to dna damage: implication for their role in tumorigenesis.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/f61b9e16b56d43aba5b5ddd2df35e5b1
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Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis.

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