ScholarWorks@중앙대학교

초록

Karyopherin-α3 (KPNA3), a karyopherin- α isoform, is intimatelyassociated with metastatic progression via epithelial-mesenchymaltransition (EMT). However, the molecular mechanismunderlying how KPNA3 acts as an EMT inducer remains to beelucidated. In this report, we identified that KPNA3 was significantlyupregulated in cancer cells, particularly in triple-negativebreast cancer, and its knockdown resulted in the suppressionof cell proliferation and metastasis. The comprehensivetranscriptome analysis from KPNA3 knockdown cells indicatedthat KPNA3 is involved in the regulation of numerous EMTrelatedgenes, including the downregulation of GATA3 andE-cadherin and the up-regulation of HAS2. Moreover, it wasfound that KPNA3 EMT-mediated metastasis can be achievedby TGF-β or AKT signaling pathways; this suggests that thenovel independent signaling pathways KPNA3-TGF-β-GATA3-HAS2/E-cadherin and KPNA3-AKT-HAS2/E-cadherin are involvedin the EMT-mediated progress of TNBC MDA-MB-231 cells. These findings provide new insights into the divergent EMTinducibility of KPNA3 according to cell and cancer type.

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