Research Papers:

MEK1 signaling promotes self-renewal and tumorigenicity of liver cancer stem cells via maintaining SIRT1 protein stabilization

Jiamin Cheng, Chungang Liu, Limei Liu, Xuejiao Chen, Juanjuan Shan, Junjie Shen, Wei Zhu and Cheng Qian _

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Oncotarget. 2016; 7:20597-20611. https://doi.org/10.18632/oncotarget.7972

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Jiamin Cheng1, Chungang Liu1, Limei Liu1, Xuejiao Chen1, Juanjuan Shan1, Junjie Shen1, Wei Zhu1, Cheng Qian1

1Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

Correspondence to:

Cheng Qian, e-mail: [email protected]

Keywords: hepatocellular carcinoma (HCC), cancer stem cells (CSCs), MEK1 signaling, SIRT1, proteasome degradation

Received: November 05, 2015     Accepted: February 02, 2016     Published: March 07, 2016


Hepatocellular carcinoma (HCC) is the third leading cause of cancer death. This high mortality has been commonly attributed to the presence of residual cancer stem cells (CSCs). Meanwhile, MEK1 signaling is regarded as a key molecular in HCC maintenance and development. However, nobody has figured out the particular mechanisms that how MEK1 signaling regulates liver CSCs self-renewal. In this study, we show that inhibition or depletion of MEK1 can significantly decrease liver CSCs self-renewal and tumor growth both in vitro and vivo conditions. Furthermore, we demonstrate that MEK1 signaling promotes liver CSCs self-renewal and tumorigenicity by maintaining SIRT1 level. Mechanistically, MEK1 signaling keeps SIRT1 protein stabilization through activating SIRT1 ubiquitination, which inhibits proteasomal degradation. Clinical analysis shows that patients co-expression of MEK1 and SIRT1 are associated with poor survival. Our finding indicates that MEK1-SIRT1 can act as a novel diagnostic biomarker and inhibition of MEK1 may be a viable therapeutic option for targeting liver CSCs treatment.

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