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ASPP2 suppresses tumour growth and stemness characteristics in HCC by inhibiting Warburg effect via WNT/β-catenin/HK2 axis |
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| Authors: | Beibei Liang Yuan Jiang Shaohua Song Wei Jing Hao Yang Li Zhao Ya Chen Qiqi Tang Xuhui Li Lisha Zhang Haili Bao Gang Huang Jian Zhao |
| Institution: | 1. Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, China;2. Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, China
Medical Engineering Department, The Affiliated Hospital of QingDao University, Qingdao, Shandong, China Contribution: Data curation (equal), ?Investigation (equal), Methodology (equal), Writing - original draft (equal);3. Liver Transplantation Center, Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Contribution: Resources (equal), Supervision (equal);4. Department of Surgery, Changhai Hospital, Navy Military Medical University, Shanghai, China Contribution: Resources (equal);5. Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, China Contribution: Data curation (equal), Methodology (equal);6. Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Contribution: Resources (equal);7. Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, China Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China Contribution: ?Investigation (equal);8. Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, China Contribution: ?Investigation (equal), Software (equal);9. Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, China Contribution: Methodology (equal);10. Department of Organ Transplantation, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, China Contribution: Resources (equal) |
| Abstract: | Abnormal energy metabolism is one of the characteristics of tumours. In the last few years, more and more attention is being paid to the role and regulation of tumour aerobic glycolysis. Cancer cells display enhanced aerobic glycolysis, also known as the Warburg effect, whereby tumour cells absorb glucose to produce a large amount of lactic acid and energy under aerobic conditions to favour tumour proliferation and metastasis. In this study, we report that the haploinsufficient tumour suppressor ASPP2, can inhibit HCC growth and stemness characteristics by regulating the Warburg effect through the WNT/β-catenin pathway. we performed glucose uptake, lactate production, pyruvate production, ECAR and OCR assays to verify ASPP2 can inhibit glycolysis in HCC cells. The expression of ASPP2 and HK2 was significantly inversely correlated in 80 HCC tissues. Our study reveals downregulation of ASPP2 can promote the aerobic glycolysis metabolism pathway, increasing HCC proliferation, glycolysis metabolism, stemness and drug resistance. This ASPP2-induced inhibition of glycolysis metabolism depends on the WNT/β-catenin pathway. ASPP2-regulated Warburg effect is associated with tumour progression and provides prognostic value. and suggest that may be promising as a new therapeutic strategy in HCC. |
| Keywords: | ASPP2 hepatocellular carcinoma tumour growth Warburg effect |