PMID- 26560124 OWN - NLM STAT- MEDLINE DCOM- 20160819 LR - 20191210 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 15 DP - 2015 Nov 11 TI - CIP2A overexpression induces autoimmune response and enhances JNK signaling pathway in human lung cancer. PG - 895 LID - 10.1186/s12885-015-1899-0 [doi] LID - 895 AB - 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. CONCLUSION: CIP2A is a tumor-associated autoantigen in lung cancer, which promote lung cancer proliferation partially through MKK4/7-JNK signaling pathway. FAU - Peng, Bo AU - Peng B AD - Border Biomedical Research Center & Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA. bpeng2@miners.utep.edu. FAU - Chai, Yurong AU - Chai Y AD - Border Biomedical Research Center & Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA. yrchai@live.cn. FAU - Li, Yang AU - Li Y AD - Border Biomedical Research Center & Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA. yli5@miners.utep.edu. FAU - Liu, Xinxin AU - Liu X AD - Border Biomedical Research Center & Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA. xliu2@miners.utep.edu. FAU - Zhang, Jianying AU - Zhang J AD - Border Biomedical Research Center & Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA. jzhang@utep.edu. LA - eng GR - G12 MD007592/MD/NIMHD NIH HHS/United States GR - SC1 CA166016/CA/NCI NIH HHS/United States GR - 5G12MD007592/MD/NIMHD NIH HHS/United States GR - SC1CA166016/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20151111 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Autoantibodies) RN - 0 (Autoantigens) RN - 0 (CIP2A protein, human) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (Proto-Oncogene Proteins c-jun) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) RN - EC 2.7.12.2 (MAP Kinase Kinase 7) SB - IM MH - Autoantibodies/blood/immunology MH - Autoantigens/*genetics/immunology/metabolism MH - Autoimmunity/*genetics MH - Case-Control Studies MH - Cell Line, Tumor MH - Cell Proliferation MH - *Gene Expression MH - Humans MH - Intracellular Signaling Peptides and Proteins MH - JNK Mitogen-Activated Protein Kinases/*metabolism MH - Lung Neoplasms/*etiology/*metabolism MH - MAP Kinase Kinase 4/metabolism MH - MAP Kinase Kinase 7/metabolism MH - Membrane Proteins/*genetics/immunology/metabolism MH - Proto-Oncogene Proteins c-jun/metabolism MH - *Signal Transduction PMC - PMC4642650 EDAT- 2015/11/13 06:00 MHDA- 2016/08/20 06:00 PMCR- 2015/11/11 CRDT- 2015/11/13 06:00 PHST- 2014/10/03 00:00 [received] PHST- 2015/11/03 00:00 [accepted] PHST- 2015/11/13 06:00 [entrez] PHST- 2015/11/13 06:00 [pubmed] PHST- 2016/08/20 06:00 [medline] PHST- 2015/11/11 00:00 [pmc-release] AID - 10.1186/s12885-015-1899-0 [pii] AID - 1899 [pii] AID - 10.1186/s12885-015-1899-0 [doi] PST - epublish SO - BMC Cancer. 2015 Nov 11;15:895. doi: 10.1186/s12885-015-1899-0.