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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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KPNA3 promotes epithelial-mesenchymal transition by regulating TGF-β and AKT signaling pathways in MDA-MB-231, a triple-negative breast cancer cell line

  • Jaesung Choi (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Jee-Hye Choi (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Ho Woon Lee (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Dongbeom Seo (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Gavaachimed Lkhagvasuren (Department of Science of Cultural Heritage, Graduate School, Chung-Ang University) ;
  • Jung-Woong Kim (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Sang-Beom Seo (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Kangseok Lee (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Kwang-Ho Lee (Department of Life Science, College of Natural Sciences, Chung-Ang University)
  • Received : 2022.11.08
  • Accepted : 2022.12.29
  • Published : 2023.02.28
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Abstract

Karyopherin-α3 (KPNA3), a karyopherin-α isoform, is intimately associated with metastatic progression via epithelial-mesenchymal transition (EMT). However, the molecular mechanism underlying how KPNA3 acts as an EMT inducer remains to be elucidated. In this report, we identified that KPNA3 was significantly upregulated in cancer cells, particularly in triple-negative breast cancer, and its knockdown resulted in the suppression of cell proliferation and metastasis. The comprehensive transcriptome analysis from KPNA3 knockdown cells indicated that KPNA3 is involved in the regulation of numerous EMT-related genes, including the downregulation of GATA3 and E-cadherin and the up-regulation of HAS2. Moreover, it was found that KPNA3 EMT-mediated metastasis can be achieved by TGF-β or AKT signaling pathways; this suggests that the novel independent signaling pathways KPNA3-TGF-β-GATA3-HAS2/E-cadherin and KPNA3-AKT-HAS2/E-cadherin are involved in the EMT-mediated progress of TNBC MDA-MB-231 cells. These findings provide new insights into the divergent EMT inducibility of KPNA3 according to cell and cancer type.

Keywords

Acknowledgement

This research was supported by the Chung-Ang University Graduate Research Scholarship in 2017.

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