适配器分子crk
过剩1
蛋白激酶B
PI3K/AKT/mTOR通路
葡萄糖转运蛋白
癌症研究
葡萄糖摄取
化学
糖原合酶
葛兰素史克-3
碳水化合物代谢
三氟化锡
细胞生物学
糖原
信号转导
激酶
生物
生物化学
信号转导衔接蛋白
内分泌学
胰岛素
作者
Chunmei Guo,Chao Gao,Xinxin Lv,Dongting Zhao,Frederick T. Greenaway,Lihong Hao,Ye Tian,Shuqing Liu,Ming‐Zhong Sun
摘要
Abstract Abnormal glucose metabolism may contribute to cancer progression. As a member of the CRK (v‐crk sarcoma virus CT10 oncogene homologue) adapter protein family, CRKL (CRK‐like) associated with the development and progression of various tumours. However, the exact role and underlying mechanism of CRKL on energy metabolism remain unknown. In this study, we investigated the effect of CRKL on glucose metabolism of hepatocarcinoma cells. CRKL and PI3K were found to be overexpressed in both hepatocarcinoma cells and tissues; meanwhile, CRKL up‐regulation was positively correlated with PI3K up‐regulation. Functional investigations revealed that CRKL overexpression promoted glucose uptake, lactate production and glycogen synthesis of hepatocarcinoma cells by up‐regulating glucose transporters 1 (GLUT1), hexokinase II (HKII) expression and down‐regulating glycogen synthase kinase 3β (GSK3β) expression. Mechanistically, CRKL promoted glucose metabolism of hepatocarcinoma cells via enhancing the CRKL‐PI3K/Akt‐GLUT1/HKII‐glucose uptake, CRKL‐PI3K/Akt‐HKII‐glucose‐lactate production and CRKL‐PI3K/Akt‐Gsk3β‐glycogen synthesis. We demonstrate CRKL facilitates HCC malignancy via enhancing glucose uptake, lactate production and glycogen synthesis through PI3K/Akt pathway. It provides interesting fundamental clues to CRKL‐related carcinogenesis through glucose metabolism and offers novel therapeutic strategies for hepatocarcinoma.
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