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

Hye Min Kang, Han Sun Son, Yan Hong Cui, Bu Hyun Youn, Beomseok Son, Nagendra Kumar Kaushik, Nizam Uddin, Jae Seong Lee, Jie Young Song, Neha Kaushik, Su Jae Lee

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)77794-77808
Number of pages15
JournalOncotarget
Volume8
Issue number44
DOIs
StatePublished - 2017 Jan 1

Fingerprint

phytosphingosine
Epithelial-Mesenchymal Transition
Breast Neoplasms
Neoplastic Stem Cells
Breast
Stem Cells
Sphingolipids
Immunoprecipitation
Protein Kinases
Neoplasms
Carcinogenesis
Radiotherapy
Down-Regulation
Apoptosis
Neoplasm Metastasis
Drug Therapy
Cell Line

Keywords

  • Cancer stem cells
  • Epidermal growth factor receptor
  • Epithelial-mesenchymal transition
  • Phytosphingosine

Cite this

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. / Phytosphingosine exhibits an anti-epithelial-mesenchymal transition function by the inhibition of EGFR signaling in human breast cancer cells. In: Oncotarget. 2017 ; Vol. 8, No. 44. pp. 77794-77808.
@article{1073a1fabe044a54b725e84b438f04c0,
title = "Phytosphingosine exhibits an anti-epithelial-mesenchymal transition function by the inhibition of EGFR signaling in human breast cancer cells",
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.",
keywords = "Cancer stem cells, Epidermal growth factor receptor, Epithelial-mesenchymal transition, Phytosphingosine",
author = "Kang, {Hye Min} and Son, {Han Sun} and Cui, {Yan Hong} and Youn, {Bu Hyun} and Beomseok Son and Kaushik, {Nagendra Kumar} and Nizam Uddin and Lee, {Jae Seong} and Song, {Jie Young} and Neha Kaushik and Lee, {Su Jae}",
year = "2017",
month = "1",
day = "1",
doi = "10.18632/oncotarget.20783",
language = "English",
volume = "8",
pages = "77794--77808",
journal = "Oncotarget",
issn = "1949-2553",
number = "44",

}

Kang, HM, Son, HS, Cui, YH, Youn, BH, Son, B, Kaushik, NK, Uddin, N, Lee, JS, Song, JY, Kaushik, N & Lee, SJ 2017, 'Phytosphingosine exhibits an anti-epithelial-mesenchymal transition function by the inhibition of EGFR signaling in human breast cancer cells', Oncotarget, vol. 8, no. 44, pp. 77794-77808. https://doi.org/10.18632/oncotarget.20783

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 journalArticle

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 -