ME2 Promotes Hepatocellular Carcinoma Cell Migration through Pyruvate

Cancer metastasis is still a major challenge in clinical cancer treatment. The migration and invasion of cancer cells into surrounding tissues and blood vessels is the primary step in cancer metastasis. However, the underlying mechanism of regulating cell migration and invasion are not fully understood. Here, we show the role of malic enzyme 2 (ME2) in promoting human liver cancer cell lines SK-Hep1 and Huh7 cells migration and invasion. Depletion of ME2 reduces cell migration and invasion, whereas overexpression of ME2 increases cell migration and invasion. Mechanistically, ME2 promotes the production of pyruvate, which directly binds to β-catenin and increases β-catenin protein levels. Notably, pyruvate treatment restores cell migration and invasion of ME2-depleted cells. Our findings provide a mechanistic understanding of the link between ME2 and cell migration and invasion.

[1]  P. Jiang,et al.  p53 protects against alcoholic fatty liver disease via ALDH2 inhibition , 2023, The EMBO journal.

[2]  Yinpeng Huang,et al.  LINC00491 promotes cell growth and metastasis through miR-324-5p/ROCK1 in liver cancer , 2021, Journal of translational medicine.

[3]  Z. Zeng,et al.  Malic enzyme 2 promotes the progression of hepatocellular carcinoma via increasing triglyceride production , 2021, Cancer medicine.

[4]  N. Chandel,et al.  Cancer metabolism: looking forward , 2021, Nature Reviews Cancer.

[5]  Cynthia A. Reinhart-King,et al.  Mechanoresponsive metabolism in cancer cell migration and metastasis. , 2021, Cell metabolism.

[6]  Y. Einaga,et al.  Nanodiamonds Inhibit Cancer Cell Migration by Strengthening Cell Adhesion: Implications for Cancer Treatment. , 2021, ACS applied materials & interfaces.

[7]  W. Du,et al.  NADPH levels affect cellular epigenetic state by inhibiting HDAC3–Ncor complex , 2021, Nature Metabolism.

[8]  Qiaoling Liu,et al.  NADP modulates RNA m6A methylation and adipogenesis via enhancing FTO activity , 2020, Nature Chemical Biology.

[9]  W. Cong,et al.  PPARγ Coactivator‐1α Suppresses Metastasis of Hepatocellular Carcinoma by Inhibiting Warburg Effect by PPARγ–Dependent WNT/β‐Catenin/Pyruvate Dehydrogenase Kinase Isozyme 1 Axis , 2020, Hepatology.

[10]  J. Schmutz,et al.  Light-responsive expression atlas reveals the effects of light quality and intensity in Kalanchoë fedtschenkoi, a plant with crassulacean acid metabolism , 2020, GigaScience.

[11]  Trung Hai Nguyen,et al.  Autodock Vina Adopts More Accurate Binding Poses but Autodock4 Forms Better Binding Affinity , 2019, J. Chem. Inf. Model..

[12]  P. Convertini,et al.  TCA Cycle Rewiring as Emerging Metabolic Signature of Hepatocellular Carcinoma , 2019, Cancers.

[13]  Aimin Li,et al.  RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer , 2019, Journal of experimental & clinical cancer research : CR.

[14]  C. Nguyên,et al.  Convergence of Canonical and Non-canonical Wnt Signal: Differential Kat3 Coactivator Usage , 2019, Current molecular pharmacology.

[15]  P. Jiang,et al.  MYC retards cancer cell migration through suppressing fibronectin expression. , 2019, Science bulletin.

[16]  Meichao Zhang,et al.  NMIIA promotes tumor growth and metastasis by activating the Wnt/β-catenin signaling pathway and EMT in pancreatic cancer , 2019, Oncogene.

[17]  Liang Wang,et al.  HSCs-derived COMP drives hepatocellular carcinoma progression by activating MEK/ERK and PI3K/AKT signaling pathways , 2018, Journal of experimental & clinical cancer research : CR.

[18]  Z. Selamoğlu,et al.  Malic enzyme 2 as a potential therapeutic drug target for cancer , 2018, IUBMB life.

[19]  James E. Bradner,et al.  R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m6A/MYC/CEBPA Signaling , 2018, Cell.

[20]  I. Ng,et al.  Secretory Stanniocalcin 1 promotes metastasis of hepatocellular carcinoma through activation of JNK signaling pathway. , 2017, Cancer letters.

[21]  Jacob D. Jaffe,et al.  Genetic and Proteomic Interrogation of Lower Confidence Candidate Genes Reveals Signaling Networks in β-Catenin-Active Cancers. , 2016, Cell systems.

[22]  Shih-Ming Huang,et al.  Human mitochondrial NAD(P)(+)-dependent malic enzyme participates in cutaneous melanoma progression and invasion. , 2015, The Journal of investigative dermatology.

[23]  A. Lane,et al.  Knockdown of Malic Enzyme 2 Suppresses Lung Tumor Growth, Induces Differentiation and Impacts PI3K/AKT Signaling , 2014, Scientific Reports.

[24]  H. Xin,et al.  How does cancer cell metabolism affect tumor migration and invasion? , 2013, Cell adhesion & migration.

[25]  S. Pervaiz,et al.  Redox regulation of cancer cell migration and invasion. , 2013, Mitochondrion.

[26]  Jun Yao,et al.  Loss of FBP1 by Snail-mediated repression provides metabolic advantages in basal-like breast cancer. , 2013, Cancer cell.

[27]  John M. Asara,et al.  Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway , 2013, Nature.

[28]  K. Wellen,et al.  Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence , 2012, Nature.

[29]  Katarzyna A. Broniowska,et al.  Pyruvate fuels mitochondrial respiration and proliferation of breast cancer cells: effect of monocarboxylate transporter inhibition. , 2012, The Biochemical journal.

[30]  Konrad Basler,et al.  The many faces and functions of β‐catenin , 2012, The EMBO journal.

[31]  Chi V Dang,et al.  Links between metabolism and cancer. , 2012, Genes & development.

[32]  R. Lehmann,et al.  Redox regulation of cell migration and adhesion. , 2012, Trends in cell biology.

[33]  M. V. Heiden,et al.  Targeting cancer metabolism: a therapeutic window opens , 2011, Nature Reviews Drug Discovery.

[34]  A. Aman,et al.  Wnt/beta-catenin and Fgf signaling control collective cell migration by restricting chemokine receptor expression. , 2008, Developmental cell.

[35]  G. Shulman,et al.  Cytosolic and Mitochondrial Malic Enzyme Isoforms Differentially Control Insulin Secretion* , 2007, Journal of Biological Chemistry.

[36]  E. Hinoi,et al.  Cytoprotection by pyruvate through an anti-oxidative mechanism in cultured rat calvarial osteoblasts. , 2006, Histology and histopathology.

[37]  David A. Cheresh,et al.  Role of integrins in cell invasion and migration , 2002, Nature Reviews Cancer.

[38]  A. Freedman,et al.  The metabolism of pyruvate in the tricarboxylic acid cycle. II. Tissue characteristic metabolism of pyruvate. , 1960, The Journal of biological chemistry.

[39]  Gabriela Bitencourt-Ferreira,et al.  Docking with AutoDock4. , 2019, Methods in molecular biology.

[40]  Yanling Chen.  Scratch Wound Healing Assay , 2012 .

[41]  A. Giatromanolaki,et al.  Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis in colorectal cancer , 2005, Clinical & Experimental Metastasis.