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

作者：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

来源：Oncotarget, 2017, 8(44): 77794-77808.

DOI：10.18632/oncotarget.20783

• phytosphingosine
• epithelial-mesenchymal transition
• cancer stem cells
• epidermal growth factor receptor

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.

• 出版日期2017-9-29