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-ribophytosphingosine (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, CD44high/CD24low 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.
| Original language | English |
|---|---|
| Pages (from-to) | 77794-77808 |
| Number of pages | 15 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 44 |
| DOIs | |
| State | Published - 2017 Jan 1 |
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Keywords
- Cancer stem cells
- Epidermal growth factor receptor
- Epithelial-mesenchymal transition
- Phytosphingosine
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Phytosphingosine exhibits an anti-epithelial-mesenchymal transition function by the inhibition of EGFR signaling in human breast cancer cells. / Kang, Hye Min; Son, Han Sun; Cui, Yan Hong; Youn, Bu Hyun; Son, Beomseok; Kaushik, Nagendra Kumar; Uddin, Nizam; Lee, Jae Seong; Song, Jie Young; Kaushik, Neha; Lee, Su Jae.
In: Oncotarget, Vol. 8, No. 44, 01.01.2017, p. 77794-77808.Research output: Contribution to journal › Article
TY - JOUR
T1 - Phytosphingosine exhibits an anti-epithelial-mesenchymal transition function by the inhibition of EGFR signaling in human breast cancer cells
AU - Kang, Hye Min
AU - Son, Han Sun
AU - Cui, Yan Hong
AU - Youn, Bu Hyun
AU - Son, Beomseok
AU - Kaushik, Nagendra Kumar
AU - Uddin, Nizam
AU - Lee, Jae Seong
AU - Song, Jie Young
AU - Kaushik, Neha
AU - Lee, Su Jae
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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-ribophytosphingosine (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, CD44high/CD24low 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.
AB - 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-ribophytosphingosine (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, CD44high/CD24low 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.
KW - Cancer stem cells
KW - Epidermal growth factor receptor
KW - Epithelial-mesenchymal transition
KW - Phytosphingosine
UR - http://www.scopus.com/inward/record.url?scp=85030315712&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.20783
DO - 10.18632/oncotarget.20783
M3 - Article
AN - SCOPUS:85030315712
VL - 8
SP - 77794
EP - 77808
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 44
ER -