CDK6 increases glycolysis and suppresses autophagy by mTORC1-HK2 pathway activation in cervical cancer cells.

Xiaoxi Zhang, Yunxia Sun, Siyao Cheng, Yanjing Yao, Xintao Hua, Yueyue Shi, Xiaoqin Jin, Jieli Pan, Miaofen G Hu, Pian Ying, Xiaoli Hou, Daozong Xia

Cell cycle (Georgetown, Tex.) 2022 May

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Cervical carcinoma is a leading malignant tumor among women worldwide, characterized by the dysregulation of cell cycle. Cyclin-dependent kinase 6 (CDK6) plays important roles in the cell cycle progression, cell differentiation, and tumorigenesis. However, the role of CDK6 in cervical cancer remains controversial. Here, we found that loss of CDK6 in cervical adenocarcinoma HeLa cell line inhibited cell proliferation but induced apoptosis as well as autophagy, accompanied by attenuated expression of mammalian target of rapamycin complex 1 (mTORC1) and hexokinase 2 (HK2), reduced glycolysis, and production of protein, nucleotide, and lipid. Similarly, we showed that CDK6 knockout inhibited the survival of CDK6-high CaSki but not CDK6-low SiHa cervical cancer cells by regulation of glycolysis and autophagy process. Collectively, our studies indicate that CDK6 is a critical regulator of human cervical cancer cells, especially with high CDK6 level, through its ability to regulate cellular apoptosis and metabolism. Thus, inhibition of CDK6 kinase activity could be a powerful therapeutic avenue used to treat cervical cancers.

Citation

Xiaoxi Zhang, Yunxia Sun, Siyao Cheng, Yanjing Yao, Xintao Hua, Yueyue Shi, Xiaoqin Jin, Jieli Pan, Miaofen G Hu, Pian Ying, Xiaoli Hou, Daozong Xia. CDK6 increases glycolysis and suppresses autophagy by mTORC1-HK2 pathway activation in cervical cancer cells. Cell cycle (Georgetown, Tex.). 2022 May;21(9):984-1002