Phytosphingosine exhibits an anti-epithelial–mesenchymal transition function by the inhibition of EGFR signaling in human breast cancer cellsopen access
- Authors
- Kang, Hye-Min; Son, Han-Sun; Cui, Yan-Hong; Youn, BuHyun; Son, Beomseok; Kaushik, Nagendra Kumar; Uddin, Nizam; Lee, Jae-Seong; Song, Jie-Young; Kaushik, Neha; Lee, Su-Jae
- Issue Date
- Sep-2017
- Publisher
- IMPACT JOURNALS LLC
- Keywords
- phytosphingosine; epithelial-mesenchymal transition; cancer stem cells; epidermal growth factor receptor
- Citation
- ONCOTARGET, v.8, no.44, pp.77794 - 77808
- Indexed
- SCIE
SCOPUS
- Journal Title
- ONCOTARGET
- Volume
- 8
- Number
- 44
- Start Page
- 77794
- End Page
- 77808
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/19446
- DOI
- 10.18632/oncotarget.20783
- 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.
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