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Hexokinase 2 regulates G1/S checkpoint through CDK2 in cancer-associated fibroblasts.
Hu, Jun-Wei; Sun, Pan; Zhang, Dao-Xiang; Xiong, Wu-Jun; Mi, Jun.
Afiliación
  • Hu JW; Shanghai East Hospital Affiliated to Tongji University, China; Institute of Cancer Stem Cell, Dalian Medical University, China.
  • Sun P; Department of Biochemistry & Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, China.
  • Zhang DX; Department of Biochemistry & Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, China.
  • Xiong WJ; Shanghai East Hospital Affiliated to Tongji University, China. Electronic address: xiongwujun@126.com.
  • Mi J; Department of Biochemistry & Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, China. Electronic address: jmei@sjtu.edu.cn.
Cell Signal ; 26(10): 2210-6, 2014 Oct.
Article en En | MEDLINE | ID: mdl-24780297
Hexokinase 2 (HK2), a pivotal glycolytic enzyme, is often overexpressed in tumor cells and contributes to glycolysis. Emerging evidence has suggested that glycolysis is also enhanced in cancer-associated fibroblasts (CAF). However, it is not clear whether HK2 is involved in enhanced glycolysis in CAFs or what role HK2 plays in the CAFs. In this study, both time course experiments and dose response experiments demonstrated that the protein and mRNA levels of HK2 increase in CAF cells, according to western blot and quantitative PCR analyses, respectively. Additionally, miR-182 targets the 3' UTR of HK2, and its overexpression results in the degradation of HK2 mRNA, which eventually reduces the level of HK2 protein. On the other hand, knockdown of miR-182 increased the expression of HK2. Most importantly, HK2 regulated the protein level and T14 phosphorylation of CDK2, and knockdown of HK2 resulted in a G1 phase cell cycle arrest. These observations suggest that HK2 plays important roles in glycolysis regulation and in cell cycle checkpoint activation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinasa 2 Dependiente de la Ciclina / Hexoquinasa Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Cell Signal Año: 2014 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinasa 2 Dependiente de la Ciclina / Hexoquinasa Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Cell Signal Año: 2014 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido