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Phytosphingosine exhibits an anti-epithelial–mesenchymal transition function by the inhibition of EGFR signaling in human breast cancer cells

Title
Phytosphingosine exhibits an anti-epithelial–mesenchymal transition function by the inhibition of EGFR signaling in human breast cancer cells
Author
KAUSHIKNEHA
Keywords
phytosphingosine; epithelial-mesenchymal transition; cancer stem cells; epidermal growth factor receptor
Issue Date
2017-09
Publisher
IMPACT JOURNALS LLC
Citation
ONCOTARGET, v. 8, no. 44, page. 77794-77808
Abstract
The lack of effective anti-metastatic drugs for the eradication of breast cancer stem cells within tumors, which are often resistant to chemotherapy and radiotherapy, creates a major obstacle during metastatic breast cancer therapy. Although D-ribo-phytosphingosine (PHS) is well known to activate protein kinase (MAPK)-mediated apoptosis, its possible role towards the metastasis signaling mechanisms underlying the epithelial-mesenchymal transition (EMT) remains largely unknown. In this report, we investigate the anti-metastatic potential of the natural sphingolipid PHS for the targeting of breast cancer cells as well as breast stem-like cells in vitro. We showed that PHS led to suppression of migratory potential, spheroid formation, CD44(high)/CD24(low) subpopulation as well as stem cell-and EMT-associated protein expression in basal type highly malignant breast cancer cell lines. In addition, PHS-based inhibition of EMT was attributable to the downregulation of the EGFR/JAK1/STAT3 signaling axis, as validated by immunoprecipitation assays and breast tumorigenesis mice models. This study demonstrate that PHS can target metastatic tumors with dual specificity (EMT and cancer stem-like cells) and therefore may be serve as a promising candidate for breast cancer treatments.
URI
http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=20783&path[]=66196https://repository.hanyang.ac.kr/handle/20.500.11754/115590
ISSN
1949-2553
DOI
10.18632/oncotarget.20783
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RESEARCH INSTITUTE[S](부설연구소) > THE RESEARCH INSTITUTE FOR NATURAL SCIENCES(자연과학연구소) > Articles
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