Guo Wenzheng, Kuang Yanbin, Wu Jingjing, Wen Donghua, Zhou Aiping, Liao Yueling, Song Hongyong, Xu Dongliang, Wang Tong, Jing Bo, Li Kaimi, Hu Min, Ling Jing, Wang Qi, Wu Wenjuan
Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
Front Oncol. 2020 Jan 31;10:52. doi: 10.3389/fonc.2020.00052. eCollection 2020.
Lung squamous cell carcinomas (SCCs) are highly aggressive tumors, and there is currently no effective targeted therapy owing to the lack of specific mutation targets. Compared with lung adenocarcinoma (ADCs), lung SCCs reportedly utilized higher levels of glucose metabolism to meet the anabolic and catabolic needs required to sustain rapid tumor growth. Hexokinase 2 (HK2) is an enzyme that catalyzes the rate-limit and first committed step in glucose metabolism. Here, we investigated the expression and effect of HK2 in lung SCCs. We found a significantly higher HK2 expression in lung SCCs, but not lung ADC or normal tissues. HK2 depletion or inhibition decreased the glycolysis and tumor growth via activating AMPK signaling pathway, which downregulated mTORC1 activity. Furthermore, we found an increased oxygen respiration rate compensating for HK2 depletion. Thus, metformin treatment showed combinatorial therapeutic value, which resulted in greater induction of lung SCC apoptosis and . Our study suggests that HK2 depletion in combination with metformin might be a novel effective strategy for lung SCCs therapy.
肺鳞状细胞癌（SCC）是侵袭性很强的肿瘤，由于缺乏特定的突变靶点，目前尚无有效的靶向治疗方法。据报道，与肺腺癌（ADC）相比，肺SCC利用更高水平的糖代谢来满足维持肿瘤快速生长所需的合成代谢和分解代谢需求。己糖激酶2（HK2）是一种催化糖代谢限速及首个关键步骤的酶。在此，我们研究了HK2在肺SCC中的表达及作用。我们发现肺SCC中HK2的表达显著高于肺ADC或正常组织。HK2的缺失或抑制通过激活AMPK信号通路降低糖酵解和肿瘤生长，该通路下调了mTORC1活性。此外，我们发现氧呼吸速率增加以补偿HK2的缺失。因此，二甲双胍治疗显示出联合治疗价值，导致肺SCC凋亡的诱导作用增强。我们的研究表明，HK2缺失与二甲双胍联合使用可能是肺SCC治疗的一种新型有效策略。
