Glucose Transporter 1 Promotes the Malignant Phenotype of Non-Small Cell Lung Cancer through Integrin β1/Src/FAK Signaling
Glucose Transporter 1 Promotes the Malignant Phenotype of Non-Small Cell Lung Cancer through Integrin β1/Src/FAK Signaling
复制标题
葡萄糖转运蛋白 1 通过整合素 beta 1/Src/FAK 信号传导促进非小细胞肺癌的恶性表型
DOI：
10.7150/jca.30772
复制
发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Wu, Guangping
中科院分区：
文献类型：
--
作者：
Zhao, Huanyu;Sun, Jian;Wu, Guangping
背景：葡萄糖转运蛋白1（GLUT1）是Warburg效应的主要因素，它与许多肿瘤的预后不良有关。但是，GLUT1在非小细胞肺癌（NSCLC）进展中的潜在分子机制不清楚。方法：我们使用定量实时PCR检测支气管刷样品中的GLUT1 mRNA表达检查GLUT1对NSCLC细胞增殖，迁移，侵袭和凋亡的影响。回报：我们发现，在恶性支气管支气管刷样品中，glut1的C（t）归一化值明显高于良性样品（P）
Background: Glucose transporter 1 (GLUT1) is the main factor of Warburg effect, which is associated with poor prognosis in many tumors. However, the underlying molecular mechanism of GLUT1 in the progression of non-small cell lung cancer (NSCLC) is unclear. Methods: We used quantitative real-time PCR to detect GLUT1 mRNA expression in bronchial brushing samples and performed Western Blot and biological behavior testing to check the effect of GLUT1 on NSCLC cell proliferation, migration, invasion and apoptosis. Results: We found that the C(t) normalized value of GLUT1 in malignant bronchial brushing samples was significantly higher than that in benign samples (P<0.05). GLUT1 significantly increased the expressions of cyclin A, cyclin D1, cyclin E, cyclin dependent kinase 2 (CDK2), CDK4, CDK6 and matrix metalloproteinase 2 (MMP2), but decreased the expressions of p53 and p130 in NSCLC cells. The biological behavior testing indicated that GLUT1 enhanced NSCLC cell proliferation, invasion and migration but inhibited cell apoptosis. In addition, GLUT1 upregulated the expression of integrin β1 and promoted the phosphorylation of focal adhesion kinase (FAK, phosphorylation at Tyr576/577) and Src (Src phosphorylation at Tyr530). siRNA knock down of integrin β1 expression suppressed GLUT1 induced NSCLC cell biological behavior, as well as the phosphorylation of FAK and Src. Conclusion: Taken together, our data confirms that GLUT1 promotes the malignant phenotype of NSCLC through integrin β1/Src/FAK signaling, which provides a new therapeutic target for the treatment and research of lung cancer.