title: Knockdown of creatine kinase B inhibits ovarian cancer progression by decreasing glycolysis.
abstract: Creatine kinase plays a key role in the energy homeostasis of vertebrate cells. Creatine kinase B (CKB), a cytosolic isoform of creatine kinase, shows upregulated expression in a variety of cancers. In this research, we confirmed that some ovarian cancer tissues had elevated CKB expression at the protein level. The functions of CKB in ovarian cancer progression were investigated in the ovarian cancer cell line Skov3, which has a high CKB expression. It was found that CKB knockdown inhibited Skov3 cell proliferation and induced apoptosis under hypoxia or hypoglycemia conditions. CKB depletion also sensitized Skov3 to chemotherapeutic agents. Furthermore, the CKB knockdown reduced glucose consumption and lactate production, and increased ROS production and oxygen consumption. This suggested that CKB knockdown decreased cytosolic glycolysis and resulted in a tumor suppressive metabolic state in Skov3 cells. Consequently, we found that the knockdown of CKB induced G2 arrest in cell cycle by elevating p21 expression and affected the PI3K/Akt and AMPK pathways. These findings provide new insights in the role of CKB in cancer cell survival and tumor progression. Our results also suggest that CKB depletion/inhibition in combination with chemotherapeutic agents might have synergistic effects in ovarian cancer therapy.
authors: Beijing Key Laboratory of Protein Therapeutics, School of Life Sciences, Tsinghua University, Beijing, China.
authors: Xu-Hui
authors: XH
authors: Li
authors: Xiang-Jun
authors: XJ
authors: Chen
authors: Wen-Bin
authors: WB
authors: Ou
authors: Qian
authors: Q
authors: Zhang
authors: Zhi-Rong
authors: ZR
authors: Lv
authors: Yi
authors: Y
authors: Zhan
authors: Long
authors: L
authors: Ma
authors: Tao
authors: T
authors: Huang
authors: Yong-Bin
authors: YB
authors: Yan
authors: Hai-Meng
authors: HM
authors: Zhou
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D048708:Cell Growth Processes / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003402:Creatine Kinase / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000502:physiology; D055785:Gene Knockdown Techniques; D006019:Glycolysis; D006801:Humans; D007527:Isoenzymes; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000903:Antibiotics, Antineoplastic; D007527:Isoenzymes; D004317:Doxorubicin; D003402:Creatine Kinase