RRC ID |
43992
|
著者 |
Wang CY, Chen CL, Tseng YL, Fang YT, Lin YS, Su WC, Chen CC, Chang KC, Wang YC, Lin CF.
|
タイトル |
Annexin A2 silencing induces G2 arrest of non-small cell lung cancer cells through p53-dependent and -independent mechanisms.
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ジャーナル |
J Biol Chem
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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.
|
巻・号 |
287(39)
|
ページ |
32512-24
|
公開日 |
2012-9-21
|
DOI |
10.1074/jbc.M112.351957
|
PII |
S0021-9258(20)62912-X
|
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 |
4.238
|
引用数 |
44
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
|