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The Protein Kinase Activity of NME7 Activates Wnt/ß-Catenin Signaling to Promote One-Carbon Metabolism in Hepatocellular Carcinoma.
Ren, Xinxin; Rong, Zhuoxian; Liu, Xiaoyu; Gao, Jie; Xu, Xu; Zi, Yuyuan; Mu, Yun; Guan, Yidi; Cao, Zhen; Zhang, Yuefang; Zeng, Zimei; Fan, Qi; Wang, Xitao; Pei, Qian; Wang, Xiang; Xin, Haiguang; Li, Zhi; Nie, Yingjie; Qiu, Zilong; Li, Nan; Sun, Lunquan; Deng, Yuezhen.
Afiliação
  • Ren X; Department of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha, China.
  • Rong Z; Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China.
  • Liu X; Hunan International Science and Technology Collaboration Base of Precision Medicine for Cancer, Changsha, China.
  • Gao J; Center for Molecular Imaging of Central South University, Xiangya Hospital, Changsha, China.
  • Xu X; Department of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha, China.
  • Zi Y; Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China.
  • Mu Y; Hunan International Science and Technology Collaboration Base of Precision Medicine for Cancer, Changsha, China.
  • Guan Y; Center for Molecular Imaging of Central South University, Xiangya Hospital, Changsha, China.
  • Cao Z; Department of Radiology and Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhang Y; Department of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha, China.
  • Zeng Z; Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China.
  • Fan Q; Hunan International Science and Technology Collaboration Base of Precision Medicine for Cancer, Changsha, China.
  • Wang X; Center for Molecular Imaging of Central South University, Xiangya Hospital, Changsha, China.
  • Pei Q; Department of Radiology and Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wang X; Department of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha, China.
  • Xin H; Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China.
  • Li Z; Hunan International Science and Technology Collaboration Base of Precision Medicine for Cancer, Changsha, China.
  • Nie Y; Center for Molecular Imaging of Central South University, Xiangya Hospital, Changsha, China.
  • Qiu Z; Department of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha, China.
  • Li N; Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, China.
  • Sun L; Hunan International Science and Technology Collaboration Base of Precision Medicine for Cancer, Changsha, China.
  • Deng Y; Center for Molecular Imaging of Central South University, Xiangya Hospital, Changsha, China.
Cancer Res ; 82(1): 60-74, 2022 01 01.
Article em En | MEDLINE | ID: mdl-34764205
Metabolic reprogramming by oncogenic signaling is a hallmark of cancer. Hyperactivation of Wnt/ß-catenin signaling has been reported in hepatocellular carcinoma (HCC). However, the mechanisms inducing hyperactivation of Wnt/ß-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/ß-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 GSK3ß to promote ß-catenin activation. Furthermore, MTHFD2, the key enzyme in one-carbon metabolism, was a target gene of ß-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, ß-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/ß-catenin signaling and one-carbon metabolism, suggesting NME7 and MTHFD2 as potential therapeutic targets for HCC. SIGNIFICANCE: The identification of NME7 as an activator of Wnt/ß-catenin signaling and MTHFD2 expression in HCC reveals a mechanism regulating one-carbon metabolism and potential therapeutic strategies for treating this disease.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Carbono / Núcleosídeo-Difosfato Quinase / Carcinoma Hepatocelular / Beta Catenina / Via de Sinalização Wnt / Neoplasias Hepáticas Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Carbono / Núcleosídeo-Difosfato Quinase / Carcinoma Hepatocelular / Beta Catenina / Via de Sinalização Wnt / Neoplasias Hepáticas Idioma: En Ano de publicação: 2022 Tipo de documento: Article