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Article

Annexin A2 regulates glioma cell proliferation through the STAT3‑cyclin D1 pathway

  • Authors:
    • Ling Chen
    • Ling Lin
    • Na Xian
    • Zhihong Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Molecular Biology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350108, P.R. China, Department of Cell Biology and Genetics, The School of Basic Medical Sciences; 3Fujian Provincial Key Laboratory of Neuroglia and Disease, Fujian Medical University, Fuzhou, Fujian 350108, P.R. China
  • Pages: 399-413
    |
    Published online on: May 9, 2019
       https://doi.org/10.3892/or.2019.7155
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Abstract

Annexin A2 (ANXA2) acts as a calcium‑dependent phospholipid‑binding protein that is widely expressed in vertebrate cells and has abnormally high expression in various tumor cells. However, the detailed molecular mechanism underlying the effects of ANXA2 on glioma cells remains unclear. The present study aimed to investigate the role and underlying molecular mechanisms of ANXA2 in glioma cell proliferation. The results revealed that knockdown of ANXA2 inhibited the proliferation of U251 and U87 glioma cell lines and decreased phosphorylated (p) signal transducer and activator of transcription 3 (STAT3)(Y705) and cyclin D1 expression, leading to impedance of the G1‑to‑S phase transition. Furthermore, it was suggested that ANXA2 may regulate pSTAT3(Y705) levels through direct binding with STAT3, thereby affecting STAT3‑cyclin D1 pathway‑mediated cell proliferation. When ANXA2 was re‑expressed in ANXA2‑knockdown cells, the expression of pSTAT3(Y705) and cyclin D1 was restored. Furthermore, overexpression of ANXA2 significantly promoted the proliferation of U251 cells, as determined by an MTT assay and a tumor formation assay in nude mice, but had no statistically significant effect on colony formation rate, cell cycle progression or the STAT3‑cyclin D1 pathway, suggesting that endogenous ANXA2 may be redundant. Additionally, the present study provided evidence that the overexpression of ANXA2 enhanced the expression of pSTAT3(Y705) in the presence of epidermal growth factor (EGF), indicating that the proliferation‑promoting effect of ANXA2 may be due to the accumulation and synergistic effect of paracrine EGF. Taken together, the present results indicated that ANXA2 may affect the proliferation of human glioma cells through the STAT3‑cyclin D1 pathway via direct interaction with STAT3 in U251 and U87 glioma cells. ANXA2 was redundant in this pathway, but positive synergy was revealed to exist between ANXA2 and EGF.
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Copy and paste a formatted citation
Spandidos Publications style
Chen L, Lin L, Xian N and Zheng Z: Annexin A2 regulates glioma cell proliferation through the STAT3‑cyclin D1 pathway. Oncol Rep 42: 399-413, 2019.
APA
Chen, L., Lin, L., Xian, N., & Zheng, Z. (2019). Annexin A2 regulates glioma cell proliferation through the STAT3‑cyclin D1 pathway. Oncology Reports, 42, 399-413. https://doi.org/10.3892/or.2019.7155
MLA
Chen, L., Lin, L., Xian, N., Zheng, Z."Annexin A2 regulates glioma cell proliferation through the STAT3‑cyclin D1 pathway". Oncology Reports 42.1 (2019): 399-413.
Chicago
Chen, L., Lin, L., Xian, N., Zheng, Z."Annexin A2 regulates glioma cell proliferation through the STAT3‑cyclin D1 pathway". Oncology Reports 42, no. 1 (2019): 399-413. https://doi.org/10.3892/or.2019.7155
Copy and paste a formatted citation
x
Spandidos Publications style
Chen L, Lin L, Xian N and Zheng Z: Annexin A2 regulates glioma cell proliferation through the STAT3‑cyclin D1 pathway. Oncol Rep 42: 399-413, 2019.
APA
Chen, L., Lin, L., Xian, N., & Zheng, Z. (2019). Annexin A2 regulates glioma cell proliferation through the STAT3‑cyclin D1 pathway. Oncology Reports, 42, 399-413. https://doi.org/10.3892/or.2019.7155
MLA
Chen, L., Lin, L., Xian, N., Zheng, Z."Annexin A2 regulates glioma cell proliferation through the STAT3‑cyclin D1 pathway". Oncology Reports 42.1 (2019): 399-413.
Chicago
Chen, L., Lin, L., Xian, N., Zheng, Z."Annexin A2 regulates glioma cell proliferation through the STAT3‑cyclin D1 pathway". Oncology Reports 42, no. 1 (2019): 399-413. https://doi.org/10.3892/or.2019.7155
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