American Association for Cancer Research
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Table S4 from The Protein Kinase Activity of NME7 Activates Wnt/β-Catenin Signaling to Promote One-Carbon Metabolism in Hepatocellular Carcinoma

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posted on 2023-03-31, 05:07 authored by Xinxin Ren, Zhuoxian Rong, Xiaoyu Liu, Jie Gao, Xu Xu, Yuyuan Zi, Yun Mu, Yidi Guan, Zhen Cao, Yuefang Zhang, Zimei Zeng, Qi Fan, Xitao Wang, Qian Pei, Xiang Wang, Haiguang Xin, Zhi Li, Yingjie Nie, Zilong Qiu, Nan Li, Lunquan Sun, Yuezhen Deng

Supplemental Table 4 Correlation between the mRNA level of NME7 and the clinical features of HCC.

Funding

National Natural Science Foundation of China

Hunan Provincial Science and Technology Department

China postdoctoral science foundation for COVID-19 prevention and control

Chinese academy of medical sciences

Research program from Department of Science and Technology of Guizhou

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ARTICLE ABSTRACT

Metabolic reprogramming by oncogenic signaling is a hallmark of cancer. Hyperactivation of Wnt/β-catenin signaling has been reported in hepatocellular carcinoma (HCC). However, the mechanisms inducing hyperactivation of Wnt/β-catenin signaling and strategies for targeting this pathway are incompletely understood. In this study, we find nucleoside diphosphate kinase 7 (NME7) to be a positive regulator of Wnt/β-catenin signaling. Upregulation of NME7 positively correlated with the clinical features of HCC. Knockdown of NME7 inhibited HCC growth in vitro and in vivo, whereas overexpression of NME7 cooperated with c-Myc to drive tumorigenesis in a mouse model and to promote the growth of tumor-derived organoids. Mechanistically, NME7 bound and phosphorylated serine 9 of GSK3β to promote β-catenin activation. Furthermore, MTHFD2, the key enzyme in one-carbon metabolism, was a target gene of β-catenin and mediated the effects of NME7. Tumor-derived organoids with NME7 overexpression exhibited increased sensitivity to MTHFD2 inhibition. In addition, expression levels of NME7, β-catenin, and MTHFD2 correlated with each other and with poor prognosis in patients with HCC. Collectively, this study emphasizes the crucial roles of NME7 protein kinase activity in promoting Wnt/β-catenin signaling and one-carbon metabolism, suggesting NME7 and MTHFD2 as potential therapeutic targets for HCC. The identification of NME7 as an activator of Wnt/β-catenin signaling and MTHFD2 expression in HCC reveals a mechanism regulating one-carbon metabolism and potential therapeutic strategies for treating this disease.

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