Pyruvate kinase M2 mediated Hyaluronan-CD44 downstream signaling pathway to promotes progression of HCC
Background Hyaluronan is expressed in hepatocellular carcinoma (HCC) as HCC generally arises from a cirrhotic liver in which excessive production and accumulation of HA leads to developing cirrhosis.Though it has been suggested HA is involved in progression of HCC, the mechanisms underlying the connection between HA and HCC progression are unclear.Since increased aerobic glycolysis is a metabolic trait of malignant cells and HA-CD44 can modulate glucose metabolism, we aim to investigat the roles of PKM2, a key enzyme in glucose metabolism, in the HA-CD44 axis facilitated the progress of HCC.Methods The effects of HA on HCCs proliferation, metastasis potential and aerobic glycolysis switch were investigated.Lentiviruses transfections were performed to establish PKM2 silenced, over-expressed, or mutated HCC cell lines, which enabled the role of PKM2 in HA-induced HCC progression and its underlying mechanism to be systematically dissected.Furthermore, the expression pattern and the relationship of HA and PKM2 in 105 human HCC liver tissues were examined.Result PKM2 was required for HA-promoted HCC progression, which was not modulated by PKM2 kinase activity but by nuclear translocation of PKM2.PKM2 translocation was Erk (Thr202/Tyr204) phosphorylation dependent, which functioned at the downstream of HA-CD44 binding.Furthermore, elevated HA expression significantly correlated with PKM2 nuclear location and was an independent factors predicting poor HCC prognosis.Conclusion PKM2 nuclear translocation is required for mediating the described HA biological effects on HCC progression and our results imply that inhibition of HA may have therapeutic value in treating HCC.
Hepatocellular carcinoma Hyaluronan,CD44 Pyruvate Kinase M2
Jinghuan Li Yingcong Wang Rongrong Yao Rui Zhang Chengdong Qin Yan Wang Xiaoying Xie Lan Zhang Yanhong Wang Zhenggang Ren
Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education;Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
国内会议
重庆
英文
328-333
2016-05-06（万方平台首次上网日期，不代表论文的发表时间）