Oncotarget

Research Papers:

SIRT1 increases YAP- and MKK3-dependent p38 phosphorylation in mouse liver and human hepatocellular carcinoma

Yulan Wang _, Ran Cui, Xiao Zhang, Yongxia Qiao, Xiangfan Liu, Yefei Chang, Yongchun Yu, Fenyong Sun and Jiayi Wang

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Oncotarget. 2016; 7:11284-11298. https://doi.org/10.18632/oncotarget.7022

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Abstract

Yulan Wang1,*, Ran Cui2,*, Xiao Zhang1, Yongxia Qiao3, Xiangfan Liu4, Yefei Chang5, Yongchun Yu6, Fenyong Sun1, Jiayi Wang1,7

1Department of Clinical Laboratory Medicine, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, 200072, China

2Department of Oncology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, 200072, China

3School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China

4Faculty of Medical Laboratory Science, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China

5Department of Clinical Laboratory Medicine, Third People’s Hospital of Yunnan Province, Kunming, 650011, Yunnan Province, China

6Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai TCM University, Shanghai, 200071, China

7Advanced Institute of Translational Medicine, Tongji University, Shanghai, 200092, China

*These authors have contributed equally to this work

Correspondence to:

Yongchun Yu, e-mail: [email protected]

Fenyong Sun, e-mail: [email protected]

Jiayi Wang, e-mail: [email protected]

Keywords: cell proliferation, liver cancer, RNA polymerase II, promoter, survival

Received: August 06, 2015     Accepted: January 13, 2016     Published: January 25, 2016

ABSTRACT

Both oncoprotein and tumor-suppressor activity have been reported for SIRTUIN1 (SIRT1) and p38 in many types of cancer. The effect of SIRT1 on p38 phosphorylation (p-p38) remains controversial and may be organ- and cell-specific. We found that SIRT1 is essential for maintaining liver size and weight in mice. SIRT1 levels were elevated in human HCC compared to adjacent normal liver tissue, and its expression correlated positively with p-p38 levels. Additionally, SIRT1-activated p38 increased liver cancer malignancy. SIRT1 increased phosphorylation and nuclear accumulation of p38, possibly by increasing MKK3 expression. SIRT1 also induced YAP expression, which in turn increased MKK3 transcription. Positive correlations between SIRT1, YAP, MKK3, and p-p38 levels indicate that blocking their activity may prove helpful in treating HCC.


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