Annexin A2 silencing induces G2 arrest of non-small cell lung cancer cells through p53-dependent and -independent mechanisms

Chi Yun Wang, Chia Ling Chen, Yau Lin Tseng, Yi Ting Fang, Yee Shin Lin, Wu Chou Su, Chien Chin Chen, Kung Chao Chang, Yi Ching Wang, Chiou Feng Lin

Research output: Contribution to journalArticle

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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 G2phase. Unexpectedly, ANXA2 silencing increased the expression of p53 and its downstream genes, which resulted in p53-dependent and -independent G2 arrest. Aberrant JNK inactivation, which was observed in ANXA2-deficient cells, inhibited cell proliferation following G2 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.

Original languageEnglish
Pages (from-to)32512-32524
Number of pages13
JournalJournal of Biological Chemistry
Volume287
Issue number39
DOIs
Publication statusPublished - Sep 21 2012

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Annexin A2
Annexins
Non-Small Cell Lung Carcinoma
Cells
Cell proliferation
Cell Proliferation
Cell Cycle
Transcription
Cytotoxicity
Cell Cycle Checkpoints
Tumors
Neoplasms
Genes
Defects

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Annexin A2 silencing induces G2 arrest of non-small cell lung cancer cells through p53-dependent and -independent mechanisms. / Wang, Chi Yun; Chen, Chia Ling; Tseng, Yau Lin; Fang, Yi Ting; Lin, Yee Shin; Su, Wu Chou; Chen, Chien Chin; Chang, Kung Chao; Wang, Yi Ching; Lin, Chiou Feng.

In: Journal of Biological Chemistry, Vol. 287, No. 39, 21.09.2012, p. 32512-32524.

Research output: Contribution to journalArticle

Wang, Chi Yun ; Chen, Chia Ling ; Tseng, Yau Lin ; Fang, Yi Ting ; Lin, Yee Shin ; Su, Wu Chou ; Chen, Chien Chin ; Chang, Kung Chao ; Wang, Yi Ching ; Lin, Chiou Feng. / Annexin A2 silencing induces G2 arrest of non-small cell lung cancer cells through p53-dependent and -independent mechanisms. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 39. pp. 32512-32524.
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