HKDC1 promotes the tumorigenesis and glycolysis in lung adenocarcinoma via regulating AMPK/mTOR signaling pathway
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PRIMARY RESEARCH
Cancer Cell International Open Access
HKDC1 promotes the tumorigenesis and glycolysis in lung adenocarcinoma via regulating AMPK/mTOR signaling pathway Xinyu Wang†, Bowen Shi†, Yue Zhao†, Qijue Lu, Xiang Fei, Chaojing Lu, Chunguang Li* and Hezhong Chen*
Abstract Background: Hexokinase domain component 1 (HKDC1) plays an oncogenic role in certain types of cancer, such as lymphoma, liver cancer, and breast cancer. Previous bioinformatics study revealed that HKDC1 was significantly upregulated in lung adenocarcinoma (LUAD). However, its biological functions and potential mechanism in LUAD have not been studied. Methods: We performed bioinformatics analysis, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and a series of functional assays in vitro and in vivo to investigate the roles of HKDC1 in LUAD. Results: We discovered that HKDC1 was highly expressed in LUAD tissues and cell lines, and the positive expression of HKDC1 was correlated with aberrant clinicopathological characteristics in LUAD patients. Furthermore, HKDC1 could serve as a prognostic predictor for LUAD patients. Overexpression of HKDC1 promoted proliferation, migration, invasion, glycolysis, EMT and tumorigenicity, whereas knockdown of HKDC1 produced the opposite functional effects. Mechanistically, HKDC1 could regulate the AMPK/mTOR signaling pathway to perform its biological function. Conclusions: Our findings suggest that HKDC1 plays an oncogenic role in LUAD. Targeting this gene may provide a promising therapeutic target to delay LUAD progression. Keywords: HKDC1, Tumorigenesis, Lung adenocarcinoma, AMPK/mTOR signaling pathway Background Lung cancer ranks first among all malignant tumors in terms of morbidity and mortality, posing a major threat to human health [1, 2]. Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer, accounting for 30–35% of primary lung cancers [3]. Although tremendous efforts have been devoted to fighting against lung cancer, limited improvement in survival has been achieved. Recently, molecular targeted therapy has shown promising results in treating LUAD [4–6], *Correspondence: [email protected]; [email protected] † Xinyu Wang, Bowen Shi and Yue Zhao contributed equally to this work Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
prompting researchers to explore new molecular mechanisms in LUAD. Aerobic glycolysis, also known as Warburg effect, refers to the conversion of glucose into lactate in cancer cells even under sufficient oxygen conditions [7]. Accumulating evidence has demonstrated that glycolysis contributes to tumor growth and metastasis through such unique metabolic pathway. Herein, it is a new strategy to delay tumor progression by inhibiting glycolysis in cancer cells [8]. Hexokinases (HKs) are a family of enzymes that catalyze the first step in glucose metabolism by phosphorylating glucose to glucose-6-phosphatase of glucose utilization [9]
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