Oncotarget

Research Papers:

Gankyrin sustains PI3K/GSK-3β/β-catenin signal activation and promotes colorectal cancer aggressiveness and progression

Feng He, Huacui Chen, Ping Yang, Qianlong Wu, Tong Zhang, Chengxing Wang, Jianchang Wei, Zhuanpeng Chen, He Hu, Wanglin Li and Jie Cao _

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Oncotarget. 2016; 7:81156-81171. https://doi.org/10.18632/oncotarget.13215

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Abstract

Feng He1,2,*, Huacui Chen1,*, Ping Yang1,*, Qianlong Wu1, Tong Zhang1, Chengxing Wang1, Jianchang Wei1, Zhuanpeng Chen1, He Hu1, Wanglin Li1, Jie Cao1

1Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China

2Department of Pathology, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, Connecticut 06520, USA

*These authors contributed equally to this work

Correspondence to:

Wanglin Li, email: [email protected]

Jie Cao, email: [email protected]

Keywords: gankyrin, colorectal cancer, metastasis, PI3K/Akt signaling, Wnt/β-catenin signaling

Received: July 06, 2016     Accepted: November 02, 2016     Published: November 08, 2016

ABSTRACT

High levels of angiogenesis, metastasis and chemoresistance are major clinical features of colorectal cancer (CRC), a lethal disease with a high incidence worldwide. Aberrant activation of Wnt/β-catenin pathway contributes to CRC progression. However, little is known about regulatory mechanisms of the β-catenin activity in cancer progression. Here we report that Gankyrin was markedly upregulated in primary tumor tissues from CRC patients and was associated with poor survival. Moreover, we demonstrated that overexpressing Gankyrin promoted, while knockdown of Gankyrin impaired, the aggressive phenotype of proliferation, angiogenesis, chemoresistance and metastasis of CRC cells both in vitro and in vivo. Importantly, we found a unique molecular mechanism of Gankyrin in CRC cells signaling transduction, that regulated the cross-talk between PI3K/Akt and Wnt/β-catenin signaling pathways, sustaining PI3K/GSK-3β/β-catenin signal activation in CRC. Therefore, these findings not only reveal a mechanism that promotes aggressiveness and progression in CRC, but also provide insight into novel molecular targets for antitumor therapy in CRCs.


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