title: Annexin A2 silencing induces G2 arrest of non-small cell lung cancer cells through p53-dependent and -independent mechanisms.
abstract: Annexin A2 (ANXA2) overexpression is required for cancer cell proliferation; however, the molecular mechanisms underlying ANXA2-mediated regulation of the cell cycle are still unknown. ANXA2 is highly expressed in non-small cell lung cancer (NSCLC) and is positively correlated with a poor prognosis. NSCLC A549 cells lacking ANXA2 exhibited defects in tumor growth in vivo and in cell proliferation in vitro without cytotoxicity. ANXA2 knockdown induced cell cycle arrest at G(2) phase. Unexpectedly, ANXA2 silencing increased the expression of p53 and its downstream genes, which resulted in p53-dependent and -independent G(2) arrest. Aberrant JNK inactivation, which was observed in ANXA2-deficient cells, inhibited cell proliferation following G(2) arrest. A lack of ANXA2 caused a loss of JNK-regulated c-Jun expression, resulting in an increase in p53 transcription. These results demonstrate a novel role for ANXA2 in NSCLC cell proliferation by facilitating the cell cycle partly through the regulation of p53 via JNK/c-Jun.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Chi-Yun
authors.initials: CY
authors.lastname: Wang
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chen
authors.forename: Yau-Lin
authors.initials: YL
authors.lastname: Tseng
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Fang
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Su
authors.forename: Chien-Chin
authors.initials: CC
authors.lastname: Chen
authors.forename: Kung-Chao
authors.initials: KC
authors.lastname: Chang
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Wang
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059565:G2 Phase Cell Cycle Checkpoints; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D016755:Proto-Oncogene Proteins c-jun; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048670:MAP Kinase Kinase 4