title: Overexpression and small molecule-triggered downregulation of CIP2A in lung cancer.
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer deaths worldwide, with a five-year overall survival rate of only 15%. Cancerous inhibitor of PP2A (CIP2A) is a human oncoprotein inhibiting PP2A in many human malignancies. However, whether CIP2A can be a new drug target for lung cancer is largely unclear.
  
  
  RESULTS
  Normal and malignant lung tissues were derived from 60 lung cancer patients from southern China. RT-PCR, Western blotting and immunohistochemistry were used to evaluate the expression of CIP2A. We found that among the 60 patients, CIP2A was undetectable or very low in paratumor normal tissues, but was dramatically elevated in tumor samples in 38 (63.3%) patients. CIP2A overexpression was associated with cigarette smoking. Silencing CIP2A by siRNA inhibited the proliferation and clonogenic activity of lung cancer cells. Intriguingly, we found a natural compound, rabdocoetsin B which is extracted from a Traditional Chinese Medicinal herb Rabdosia coetsa, could induce down-regulation of CIP2A and inactivation of Akt pathway, and inhibit proliferation and induce apoptosis in a variety of lung cancer cells.
  
  
  CONCLUSIONS
  Our findings strongly indicate that CIP2A could be an effective target for lung cancer drug development, and the therapeutic potentials of CIP2A-targeting agents warrant further investigation.
authors.affiliation: Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Zhe-Sheng
authors.initials: ZS
authors.lastname: Wen
authors.forename: Zi
authors.initials: Z
authors.lastname: Liu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Chen
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Liu
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Pu
authors.forename: Wei-Lie
authors.initials: WL
authors.lastname: Xiao
authors.forename: Han-Dong
authors.initials: HD
authors.lastname: Sun
authors.forename: Guang-Biao
authors.initials: GB
authors.lastname: Zhou
mesh_terms: D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects
chemical_list: D001324:Autoantigens; C500266:CIP2A protein, human; D004224:Diterpenes; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C557752:rabdocoetsin B; D051057:Proto-Oncogene Proteins c-akt