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ATX‑LPA axis facilitates estrogen‑induced endometrial cancer cell proliferation via MAPK/ERK signaling pathway

  • Authors:
    • Guo Zhang
    • Yuan Cheng
    • Qi Zhang
    • Xiaoping Li
    • Jingwei Zhou
    • Jianliu Wang
    • Lihui Wei
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology and Obstetrics, Peking University People's Hospital, Beijing 100044, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4245-4252
    |
    Published online on: January 8, 2018
       https://doi.org/10.3892/mmr.2018.8392
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Abstract

Autotaxin (ATX) is a key enzyme that converts lysophosphatidylcholine to lysophosphatidic acid (LPA). ATX is a crucial factor that facilitates cancer progression; however, the effect of ATX on endometrial cancer has not been explored. The aim of the present study was to investigate the role of ATX in the progression of endometrial cancer. The immunohistochemical results revealed higher protein expression levels of ATX and LPA receptors (LPA 1, 2 and 3) in human endometrial cancer tissue than in non‑carcinoma tissue. In addition, reverse transcription‑quantitative polymerase chain reaction and western blotting analysis demonstrated that ATX and LPA receptor mRNA and protein expression was greater in Ishikawa cells, which are positive for estrogen receptor (ER), than in Hec‑1A cells that exhibit low ER expression. Short interfering RNA knockdown of ATX in Ishikawa cells led to decreased cell proliferation and cell colony number, as determined by Cell Counting kit‑8 and colony formation assays. Estrogen stimulated ATX mRNA expression. Inhibition of ATX decreased estrogen and LPA‑induced cell proliferation. High LPA levels markedly elevated the phosphorylation levels of extracellular signal‑regulated kinase (ERK). ATX downregulation moderately decreased estrogen‑ and LPA‑induced phosphorylation of ERK. In addition, the ERK inhibitor, PD98059, reduced cell proliferation with estrogen, ATX and LPA treatment. The present study suggested that the ATX‑LPA axis may facilitate estrogen‑induced cell proliferation in endometrial cancer via the mitogen‑activated protein kinase/ERK signaling pathway. The present study may provide ideas and an experimental basis for clinicians to identify new molecular targeted drugs for the treatment of endometrial cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang G, Cheng Y, Zhang Q, Li X, Zhou J, Wang J and Wei L: ATX‑LPA axis facilitates estrogen‑induced endometrial cancer cell proliferation via MAPK/ERK signaling pathway. Mol Med Rep 17: 4245-4252, 2018.
APA
Zhang, G., Cheng, Y., Zhang, Q., Li, X., Zhou, J., Wang, J., & Wei, L. (2018). ATX‑LPA axis facilitates estrogen‑induced endometrial cancer cell proliferation via MAPK/ERK signaling pathway. Molecular Medicine Reports, 17, 4245-4252. https://doi.org/10.3892/mmr.2018.8392
MLA
Zhang, G., Cheng, Y., Zhang, Q., Li, X., Zhou, J., Wang, J., Wei, L."ATX‑LPA axis facilitates estrogen‑induced endometrial cancer cell proliferation via MAPK/ERK signaling pathway". Molecular Medicine Reports 17.3 (2018): 4245-4252.
Chicago
Zhang, G., Cheng, Y., Zhang, Q., Li, X., Zhou, J., Wang, J., Wei, L."ATX‑LPA axis facilitates estrogen‑induced endometrial cancer cell proliferation via MAPK/ERK signaling pathway". Molecular Medicine Reports 17, no. 3 (2018): 4245-4252. https://doi.org/10.3892/mmr.2018.8392
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang G, Cheng Y, Zhang Q, Li X, Zhou J, Wang J and Wei L: ATX‑LPA axis facilitates estrogen‑induced endometrial cancer cell proliferation via MAPK/ERK signaling pathway. Mol Med Rep 17: 4245-4252, 2018.
APA
Zhang, G., Cheng, Y., Zhang, Q., Li, X., Zhou, J., Wang, J., & Wei, L. (2018). ATX‑LPA axis facilitates estrogen‑induced endometrial cancer cell proliferation via MAPK/ERK signaling pathway. Molecular Medicine Reports, 17, 4245-4252. https://doi.org/10.3892/mmr.2018.8392
MLA
Zhang, G., Cheng, Y., Zhang, Q., Li, X., Zhou, J., Wang, J., Wei, L."ATX‑LPA axis facilitates estrogen‑induced endometrial cancer cell proliferation via MAPK/ERK signaling pathway". Molecular Medicine Reports 17.3 (2018): 4245-4252.
Chicago
Zhang, G., Cheng, Y., Zhang, Q., Li, X., Zhou, J., Wang, J., Wei, L."ATX‑LPA axis facilitates estrogen‑induced endometrial cancer cell proliferation via MAPK/ERK signaling pathway". Molecular Medicine Reports 17, no. 3 (2018): 4245-4252. https://doi.org/10.3892/mmr.2018.8392
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