Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

CAMK2γ antagonizes mTORC1 activation during hepatocarcinogenesis

Oncogene volume 36, pages 2446–2456 (2017)Cite this article

Subjects

Abstract

Hepatocellular carcinoma (HCC) is one of the most deadly cancers that still lacks effective treatments. Dysregulation of kinase signaling has frequently been reported to contribute to HCC. In this study, we used bioinformatic approaches to identify kinases that regulate gene expression changes in human HCCs and two murine HCC models. We identified a role for calcium/calmodulin-dependent protein kinases II gamma isoform (CAMK2γ) in hepatocarcinogenesis. CAMK2γ−/− mice displayed severely enhanced chemical-induced hepatocarcinogenesis compared with wild-type controls. Mechanistically, CAMK2γ deletion potentiates hepatic activation of mechanistic target of rapamycin complex 1 (mTORC1), which results in hyperproliferation of hepatocytes. Inhibition of mTORC1 by rapamycin effectively attenuates the compensatory proliferation of hepatocytes in CAMK2γ−/− livers. We further demonstrated that CAMK2γ suppressed growth factor- or insulin-induced mTORC1 activation by inhibiting IRS1/AKT signaling. Taken together, our results reveal a novel mechanism by which CAMK2γ antagonizes mTORC1 activation during hepatocarcinogenesis.

This is a preview of subscription content, access via your institution

Access options

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

Accession codes

Accessions

Gene Expression Omnibus

References

  1. Thomas MB, Zhu AX . Hepatocellular carcinoma: the need for progress. J Clin Oncol 2005; 23: 2892–2899.

    Article  PubMed  Google Scholar 

  2. Maluccio M, Covey A . Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J Clin 2012; 62: 394–399.

    Article  PubMed  Google Scholar 

  3. El-Serag HB . Hepatocellular carcinoma. N Engl J Med 2011; 365: 1118–1127.

    Article  CAS  PubMed  Google Scholar 

  4. Arzumanyan A, Reis HM, Feitelson MA . Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer 2013; 13: 123–135.

    Article  CAS  PubMed  Google Scholar 

  5. He G, Karin M . NF-kappaB and STAT3—key players in liver inflammation and cancer. Cell Res 2011; 21: 159–168.

    Article  CAS  PubMed  Google Scholar 

  6. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378–390.

    Article  CAS  PubMed  Google Scholar 

  7. Bhat M, Sonenberg N, Gores GJ . The mTOR pathway in hepatic malignancies. Hepatology 2013; 58: 810–818.

    Article  CAS  PubMed  Google Scholar 

  8. Pernicova I, Korbonits M . Metformin—mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol 2014; 10: 143–156.

    Article  CAS  PubMed  Google Scholar 

  9. Liu Y, Chance MR . Integrating phosphoproteomics in systems biology. Comput struct biotechnol j 2014; 10: 90–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kim MS, Zhong J, Pandey A . Common errors in mass spectrometry-based analysis of post-translational modifications. Proteomics 2016; 16: 700–714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cretich M, Damin F, Pirri G, Chiari M . Protein and peptide arrays: recent trends and new directions. Biomol eng 2006; 23: 77–88.

    Article  CAS  PubMed  Google Scholar 

  12. Reimer U, Reineke U, Schneider-Mergener J . Peptide arrays: from macro to micro. Curr opin biotechnol 2002; 13: 315–320.

    Article  CAS  PubMed  Google Scholar 

  13. Arsenault R, Griebel P, Napper S . Peptide arrays for kinome analysis: new opportunities and remaining challenges. Proteomics 2011; 11: 4595–4609.

    Article  CAS  PubMed  Google Scholar 

  14. Chen WM, Danziger SA, Chiang JH, Aitchison JD . PhosphoChain: a novel algorithm to predict kinase and phosphatase networks from high-throughput expression data. Bioinformatics 2013; 29: 2435–2444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chen EY, Xu H, Gordonov S, Lim MP, Perkins MH, Ma'ayan A . Expression2Kinases: mRNA profiling linked to multiple upstream regulatory layers. Bioinformatics 2012; 28: 105–111.

    Article  CAS  PubMed  Google Scholar 

  16. Kramer A, Green J, Pollard J Jr., Tugendreich S . Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 2014; 30: 523–530.

    Article  PubMed  Google Scholar 

  17. Azeloglu EU, Hardy SV, Eungdamrong NJ, Chen Y, Jayaraman G, Chuang PY et al. Interconnected network motifs control podocyte morphology and kidney function. Sci signal 2014; 7: ra12.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Vasudevan HN, Soriano P . SRF regulates craniofacial development through selective recruitment of MRTF cofactors by PDGF signaling. Dev cell 2014; 31: 332–344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. De Minicis S, Seki E, Uchinami H, Kluwe J, Zhang Y, Brenner DA et al. Gene expression profiles during hepatic stellate cell activation in culture and in vivo. Gastroenterology 2007; 132: 1937–1946.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang SJ, Steijaert MN, Lau D, Schutz G, Delucinge-Vivier C, Descombes P et al. Decoding NMDA receptor signaling: identification of genomic programs specifying neuronal survival and death. Neuron 2007; 53: 549–562.

    Article  CAS  PubMed  Google Scholar 

  21. Laplante M, Sabatini DM . mTOR signaling in growth control and disease. Cell 2012; 149: 274–293.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Volarevic S, Stewart MJ, Ledermann B, Zilberman F, Terracciano L, Montini E et al. Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6. Science 2000; 288: 2045–2047.

    Article  CAS  PubMed  Google Scholar 

  23. Hell JW . CaMKII: claiming center stage in postsynaptic function and organization. Neuron 2014; 81: 249–265.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Swaminathan PD, Purohit A, Soni S, Voigt N, Singh MV, Glukhov AV et al. Oxidized CaMKII causes cardiac sinus node dysfunction in mice. J Clin Invest 2011; 121: 3277–3288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Timmins JM, Ozcan L, Seimon TA, Li G, Malagelada C, Backs J et al. Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. J clin invest 2009; 119: 2925–2941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Florian MC, Nattamai KJ, Dorr K, Marka G, Uberle B, Vas V et al. A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing. Nature 2013; 503: 392–396.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Erickson JR, Joiner ML, Guan X, Kutschke W, Yang J, Oddis CV et al. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 2008; 133: 462–474.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Midorikawa R, Takei Y, Hirokawa N . KIF4 motor regulates activity-dependent neuronal survival by suppressing PARP-1 enzymatic activity. Cell 2006; 125: 371–383.

    Article  CAS  PubMed  Google Scholar 

  29. Lachmann A, Xu H, Krishnan J, Berger SI, Mazloom AR, Ma'ayan A . ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. Bioinformatics 2010; 26: 2438–2444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lachmann A, Ma'ayan A . KEA: kinase enrichment analysis. Bioinformatics 2009; 25: 684–686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu N, Meng Z, Lou G, Zhou W, Wang X, Zhang Y et al. Hepatocarcinogenesis in FXR−/− mice mimics human HCC progression that operates through HNF1alpha regulation of FXR expression. Mol Endocrinol 2012; 26: 775–785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yang F, Huang X, Yi T, Yen Y, Moore DD, Huang W . Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res 2007; 67: 863–867.

    Article  CAS  PubMed  Google Scholar 

  33. Kim I, Morimura K, Shah Y, Yang Q, Ward JM, Gonzalez FJ . Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis 2007; 28: 940–946.

    Article  CAS  PubMed  Google Scholar 

  34. Li Z, Tuteja G, Schug J, Kaestner KH . Foxa1 and Foxa2 are essential for sexual dimorphism in liver cancer. Cell 2012; 148: 72–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 2007; 317: 121–124.

    Article  CAS  PubMed  Google Scholar 

  36. Satow R, Shitashige M, Kanai Y, Takeshita F, Ojima H, Jigami T et al. Combined functional genome survey of therapeutic targets for hepatocellular carcinoma. Clin Cancer Res 2010; 16: 2518–2528.

    Article  CAS  PubMed  Google Scholar 

  37. Smyth GK . Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat appl genet mol biol 2004; 3: 1–25.

    Article  Google Scholar 

  38. Rabinowitz KM, Wang Y, Chen EY, Hovhannisyan Z, Chiang D, Berin MC et al. Transforming growth factor beta signaling controls activities of human intestinal CD8(+)T suppressor cells. Gastroenterology 2013; 144: 601–612 e601.

    Article  CAS  PubMed  Google Scholar 

  39. Goldman A, Roy J, Bodenmiller B, Wanka S, Landry CR, Aebersold R et al. The calcineurin signaling network evolves via conserved kinase-phosphatase modules that transcend substrate identity. Mol cell 2014; 55: 422–435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rexer BN, Ham AJ, Rinehart C, Hill S, Granja-Ingram Nde M, Gonzalez-Angulo AM et al. Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition. Oncogene 2011; 30: 4163–4174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Meng Z, Li T, Ma X, Wang X, Van Ness C, Gan Y et al. Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells by targeting Ca(2)(+)/calmodulin-dependent protein kinase II. Mol Cancer Ther 2013; 12: 2067–2077.

    Article  CAS  PubMed  Google Scholar 

  42. Gu Y, Chen T, Meng Z, Gan Y, Xu X, Lou G et al. CaMKII gamma, a critical regulator of CML stem/progenitor cells, is a target of the natural product berbamine. Blood 2012; 120: 4829–4839.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Huang W, Zhang J, Washington M, Liu J, Parant JM, Lozano G et al. Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor. Mol Endocrinol 2005; 19: 1646–1653.

    Article  CAS  PubMed  Google Scholar 

  44. Meng Z, Wang X, Gan Y, Zhang Y, Zhou H, Ness CV et al. Deletion of IFNgamma enhances hepatocarcinogenesis in FXR knockout mice. J Hepatol 2012; 57: 1004–1012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Maeda S, Kamata H, Luo JL, Leffert H, Karin M . IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 2005; 121: 977–990.

    Article  CAS  PubMed  Google Scholar 

  46. Sakurai T, Maeda S, Chang L, Karin M . Loss of hepatic NF-kappa B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation. Proc Natl Acad Sci USA 2006; 103: 10544–10551.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ishiguro K, Green T, Rapley J, Wachtel H, Giallourakis C, Landry A et al. Ca2+/calmodulin-dependent protein kinase II is a modulator of CARMA1-mediated NF-kappaB activation. Mol Cell Biol 2006; 26: 5497–5508.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Si J, Collins SJ . Activated Ca2+/calmodulin-dependent protein kinase IIgamma is a critical regulator of myeloid leukemia cell proliferation. Cancer res 2008; 68: 3733–3742.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Soliman GA, Acosta-Jaquez HA, Dunlop EA, Ekim B, Maj NE, Tee AR et al. mTOR Ser-2481 autophosphorylation monitors mTORC-specific catalytic activity and clarifies rapamycin mechanism of action. J Biol Chem 2010; 285: 7866–7879.

    Article  CAS  PubMed  Google Scholar 

  50. Abdul-Ghani R, Serra V, Gyorffy B, Jurchott K, Solf A, Dietel M et al. The PI3K inhibitor LY294002 blocks drug export from resistant colon carcinoma cells overexpressing MRP1. Oncogene 2006; 25: 1743–1752.

    Article  CAS  PubMed  Google Scholar 

  51. De Fea K, Roth RA . Protein kinase C modulation of insulin receptor substrate-1 tyrosine phosphorylation requires serine 612. Biochemistry 1997; 36: 12939–12947.

    Article  CAS  PubMed  Google Scholar 

  52. Pickert G, Neufert C, Leppkes M, Zheng Y, Wittkopf N, Warntjen M et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med 2009; 206: 1465–1472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mothe I, Van Obberghen E . Phosphorylation of insulin receptor substrate-1 on multiple serine residues, 612, 632, 662, and 731, modulates insulin action. J Biol Chem 1996; 271: 11222–11227.

    Article  CAS  PubMed  Google Scholar 

  54. Illario M, Monaco S, Cavallo AL, Esposito I, Formisano P, D'Andrea L et al. Calcium-calmodulin-dependent kinase II (CaMKII) mediates insulin-stimulated proliferation and glucose uptake. Cell Signal 2009; 21: 786–792.

    Article  CAS  PubMed  Google Scholar 

  55. Whittaker S, Marais R, Zhu AX . The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 2010; 29: 4989–5005.

    Article  CAS  PubMed  Google Scholar 

  56. Wagner EF, Nebreda AR . Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 2009; 9: 537–549.

    Article  CAS  PubMed  Google Scholar 

  57. Ozcan L, Wong CC, Li G, Xu T, Pajvani U, Park SK et al. Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity. Cell Metab 2012; 15: 739–751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Feng GS . Conflicting roles of molecules in hepatocarcinogenesis: paradigm or paradox. Cancer Cell 2012; 21: 150–154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sakurai T, Maeda S, Chang L, Karin M . Loss of hepatic NF-kappa B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation. Proc Natl Acad Sci USA 2006; 103: 10544–10551.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Matter MS, Decaens T, Andersen JB, Thorgeirsson SS . Targeting the mTOR pathway in hepatocellular carcinoma: current state and future trends. J Hepatol 2014; 60: 855–865.

    Article  CAS  PubMed  Google Scholar 

  61. Calvisi DF, Wang C, Ho C, Ladu S, Lee SA, Mattu S et al. Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma. Gastroenterology 2011; 140: 1071–1083.

    Article  CAS  PubMed  Google Scholar 

  62. Horie Y, Suzuki A, Kataoka E, Sasaki T, Hamada K, Sasaki J et al. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest 2004; 113: 1774–1783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Menon S, Yecies JL, Zhang HH, Howell JJ, Nicholatos J, Harputlugil E et al. Chronic activation of mTOR complex 1 is sufficient to cause hepatocellular carcinoma in mice. Sci signal 2012; 5: ra24.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Kenerson HL, Yeh MM, Kazami M, Jiang X, Riehle KJ, McIntyre RL et al. Akt and mTORC1 have different roles during liver tumorigenesis in mice. Gastroenterology 2013; 144: 1055–1065.

    Article  CAS  PubMed  Google Scholar 

  65. Patsenker E, Schneider V, Ledermann M, Saegesser H, Dorn C, Hellerbrand C et al. Potent antifibrotic activity of mTOR inhibitors sirolimus and everolimus but not of cyclosporine A and tacrolimus in experimental liver fibrosis. J Hepatol 2011; 55: 388–398.

    Article  CAS  PubMed  Google Scholar 

  66. Zhang ZJ, Zheng ZJ, Shi R, Su Q, Jiang Q, Kip KE . Metformin for liver cancer prevention in patients with type 2 diabetes: a systematic review and meta-analysis. J clin endocrinol metab 2012; 97: 2347–2353.

    Article  CAS  PubMed  Google Scholar 

  67. Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP . Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 2005; 121: 179–193.

    Article  CAS  PubMed  Google Scholar 

  68. Zoncu R, Efeyan A, Sabatini DM . mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011; 12: 21–35.

    Article  CAS  PubMed  Google Scholar 

  69. Ma XM, Blenis J . Molecular mechanisms of mTOR-mediated translational control. Nature rev Mol cell biol 2009; 10: 307–318.

    Article  Google Scholar 

  70. Carriere A, Cargnello M, Julien LA, Gao H, Bonneil E, Thibault P et al. Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation. Curr Biol 2008; 18: 1269–1277.

    Article  CAS  PubMed  Google Scholar 

  71. Ozcan L, Cristina de Souza J, Harari AA, Backs J, Olson EN, Tabas I . Activation of calcium/calmodulin-dependent protein kinase II in obesity mediates suppression of hepatic insulin signaling. Cell Metab 2013; 18: 803–815.

    Article  CAS  PubMed  Google Scholar 

  72. Ravichandran LV, Esposito DL, Chen J, Quon MJ . Protein kinase C-zeta phosphorylates insulin receptor substrate-1 and impairs its ability to activate phosphatidylinositol 3-kinase in response to insulin. J Biol Chem 2001; 276: 3543–3549.

    Article  CAS  PubMed  Google Scholar 

  73. Boehm J, Kang MG, Johnson RC, Esteban J, Huganir RL, Malinow R . Synaptic incorporation of AMPA receptors during LTP is controlled by a PKC phosphorylation site on GluR1. Neuron 2006; 51: 213–225.

    Article  CAS  PubMed  Google Scholar 

  74. DeVries TA, Kalkofen RL, Matassa AA, Reyland ME . Protein kinase Cdelta regulates apoptosis via activation of STAT1. J Biol Chem 2004; 279: 45603–45612.

    Article  CAS  PubMed  Google Scholar 

  75. Nair JS, DaFonseca CJ, Tjernberg A, Sun W, Darnell JE Jr., Chait BT et al. Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma. Proc Natl Acad Sci USA 2002; 99: 5971–5976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. de Groot RP, den Hertog J, Vandenheede JR, Goris J, Sassone-Corsi P . Multiple and cooperative phosphorylation events regulate the CREM activator function. EMBO j 1993; 12: 3903–3911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ella E, Heim D, Stoyanov E, Harari-Steinfeld R, Steinfeld I, Pappo O et al. Specific genomic and transcriptomic aberrations in tumors induced by partial hepatectomy of a chronically inflamed murine liver. Oncotarget 2014; 5: 10318–10331.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Papa S, Zazzeroni F, Fu YX, Bubici C, Alvarez K, Dean K et al. Gadd45beta promotes hepatocyte survival during liver regeneration in mice by modulating JNK signaling. J Clin Invest 2008; 118: 1911–1923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Dr Johannes Backs for providing the Camk2γ KO mice. We also thank Dr Richard Ermel and the Animal Resource center for the technique support in animal experiments. Similarly, we thank Dr Yun Yen and Yafan Wang and the Translational Research Core for providing reagents. This work is supported in part by NCI 1R01-CA139158 and the National Natural Science Foundation of China (81270601 and 81328016).

Author information

Author notes

  1. Z Meng and X Ma: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA, USA

    Z Meng, X Ma, J Du, X Wang, Y Gu, J Zhang, X Gan, C Van Ness, X Fu, D E Schones & W Huang

  2. Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA

    X Ma, J Du, D E Schones & W Huang

  3. School of Public Health, Guangxi Medical University, Nanning, Guangxi, China

    M He

  4. Department of Hematology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Zhejiang University, Hangzhou, Zhejiang, China

    Y Gu & R Xu

  5. Cancer Institute, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    J Zhang & R Xu

  6. Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    W Han & Z Fang

  7. State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China

    X Fu

Authors
  1. Z Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. X Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M He
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Z Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. X Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C Van Ness
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. X Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. D E Schones
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. R Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. W Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to R Xu or W Huang.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Oncogene website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Meng, Z., Ma, X., Du, J. et al. CAMK2γ antagonizes mTORC1 activation during hepatocarcinogenesis. Oncogene 36, 2446–2456 (2017). https://doi.org/10.1038/onc.2016.400

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2016.400

This article is cited by

Search

Advanced search

Quick links