title: CIP2A overexpression induces autoimmune response and enhances JNK signaling pathway in human lung cancer.
abstract: BACKGROUND
  Cancerous inhibitor of PP2A (CIP2A) is a recently characterized oncoprotein, which promotes cancer cell proliferation. But the role of CIP2A in lung cancer progression is still not well understood.
  
  
  METHODS
  The expression level of CIP2A in lung cancer tissues was examined by immunohistochemistry. CIP2A-associated cell proliferation was performed by knock down or overexpression of CIP2A in lung cancer cells. Phospho-array was used to screen kinase candidates related to expression change of CIP2A. Western-blot and luciferase reporter assay were used to validate phospho-array results.
  
  
  RESULTS
  Overexpression of CIP2A in lung cancer not only triggers immune response in lung cancer patients but also promotes lung cancer cell proliferation. By phospho-array, several kinase candidates were identified, one of which is c-Jun activated kinases (JNK). The knock down of CIP2A decreased JNK phosphorylation, and the phosphorylation of downstream transcriptional factors, ATF2 and c-Jun, whose transcriptional activity were decreased as well. Furthermore, the expression level of CIP2A also affected the phosphorylation of the upstream kinase of JNK, MKK4/MKK7. At last, treatment with JNK inhibitor partially abolished CIP2A-induced cell proliferation.
  
  
  CONCLUSIONS
  CIP2A is a tumor-associated autoantigen in lung cancer, which promote lung cancer proliferation partially through MKK4/7-JNK signaling pathway.
authors.affiliation: Border Biomedical Research Center & Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA. bpeng2@miners.utep.edu.
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.affiliation: Border Biomedical Research Center & Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA. yrchai@live.cn.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Border Biomedical Research Center & Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA. yli5@miners.utep.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Border Biomedical Research Center & Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA. xliu2@miners.utep.edu.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Border Biomedical Research Center & Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA. jzhang@utep.edu.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
mesh_terms: D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000209:etiology* / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D048688:MAP Kinase Kinase 7 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016755:Proto-Oncogene Proteins c-jun; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7