Over expression of hyaluronan promotes progression of HCC via CD44-mediated pyruvate kinase M2 nuclear translocation.
Over expression of hyaluronan promotes progression of HCC via CD44-mediated pyruvate kinase M2 nuclear translocation.
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透明质酸的过度表达通过 CD44 介导的丙酮酸激酶 M2 核转位促进 HCC 的进展。
DOI：
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Zheng-Gang Ren
中科院分区：
文献类型：
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作者：
Xiao-Ying Xie;Xin Yin;Lan Zhang;Zheng-Gang Ren
透明质酸在肝细胞癌（HCC）中表达，因为HCC通常产生自肝硬化，其中HA的过度产生和积累导致发展成肝硬化。尽管HA与HCC的进展有关，但HA与HCC进展之间的联系机制尚不清楚。由于有氧糖酵解增加是恶性细胞的代谢特征，HA-CD 44可以调节葡萄糖代谢，我们的目的是研究PKM 2，葡萄糖代谢的关键酶，在HA-CD 44轴促进肝癌的进展。我们发现PKM 2是HA促进的HCC进展所必需的，这不是由PKM 2激酶活性调节的，而是由PKM 2的核转位调节的。PKM 2的转位依赖于Erk（Thr 202/Tyr 204）磷酸化，其作用于HA-CD 44结合的下游。HA的高表达与PKM 2的核定位密切相关，是预测HCC预后不良的独立因素。结论：PKM 2核转位是介导HA对HCC进展的生物学效应所必需的，我们的研究结果表明，抑制HA可能在治疗HCC中具有治疗价值。
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 investigate the roles of PKM2, a key enzyme in glucose metabolism, in the HA-CD44 axis facilitated the progress of HCC. We shown 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. In conclusions 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.
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影响因子：
8
作者：
Bourguignon, L. Y. W.;Earle, C.;Wong, G.;Spevak, C. C.;Krueger, K.
通讯作者：
Krueger, K.
DOI：
10.5061/dryad.8mc79/19
发表时间：
2014-08
期刊：
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影响因子：
--
作者：
B. Mimee;Marc‐Olivier Duceppe;Pierre-Yves Véronneau;Joël Lafond-Lapalme;Martine Jean;François Belzile
通讯作者：
B. Mimee;Marc‐Olivier Duceppe;Pierre-Yves Véronneau;Joël Lafond-Lapalme;Martine Jean;François Belzile
DOI：
10.1002/hed.22991
发表时间：
2013-04
期刊：
Head & Neck
影响因子：
--
作者：
Steven J. Wang;Christine Earle;G. Wong;L. Bourguignon
通讯作者：
Steven J. Wang;Christine Earle;G. Wong;L. Bourguignon
影响因子：
3.9
作者：
Oskarsson, Thordur
通讯作者：
Oskarsson, Thordur
影响因子：
2.8
作者：
Ni, Jie;Cozzi, Paul J.;Li, Yong
通讯作者：
Li, Yong