RRC ID 43992
Author Wang CY, Chen CL, Tseng YL, Fang YT, Lin YS, Su WC, Chen CC, Chang KC, Wang YC, Lin CF.
Title Annexin A2 silencing induces G2 arrest of non-small cell lung cancer cells through p53-dependent and -independent mechanisms.
Journal J Biol Chem
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.
Volume 287(39)
Pages 32512-24
Published 2012-9-21
DOI 10.1074/jbc.M112.351957
PII M112.351957
PMID 22859294
PMC PMC3463346
MeSH Animals Annexin A2 / genetics Annexin A2 / metabolism* Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Non-Small-Cell Lung / metabolism* Carcinoma, Non-Small-Cell Lung / pathology G2 Phase Cell Cycle Checkpoints* Gene Knockdown Techniques Gene Silencing* Humans Lung Neoplasms / genetics Lung Neoplasms / metabolism* Lung Neoplasms / pathology MAP Kinase Kinase 4 / genetics MAP Kinase Kinase 4 / metabolism Mice Mice, Inbred BALB C Mice, Nude Proto-Oncogene Proteins c-jun / genetics Proto-Oncogene Proteins c-jun / metabolism Transcription, Genetic / genetics Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism*
IF 4.106
Times Cited 44
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells