Oncotarget

Research Papers:

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, BuHyun Youn, Beomseok Son, Nagendra Kumar Kaushik, Nizam Uddin, Jae-Seong Lee, Jie-Young Song, Neha Kaushik and Su-Jae Lee _

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Oncotarget. 2017; 8:77794-77808. https://doi.org/10.18632/oncotarget.20783

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Abstract

Hye-Min Kang1,2,*, Han-Sun Son2,*, Yan-Hong Cui2, BuHyun Youn3, Beomseok Son3, Nagendra Kumar Kaushik4, Nizam Uddin2, Jae-Seong Lee1, Jie-Young Song5, Neha Kaushik2 and Su-Jae Lee2

1Department of Biological Science, College of Science, Sungkyunkwan University, Suwon, Republic of Korea

2Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Republic of Korea

3Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea

4Plasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul, Republic of Korea

5Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Su-Jae Lee, email: sj0420@hanyang.ac.kr

Neha Kaushik, email: neha.bioplasma@gmail.com

Keywords: phytosphingosine, epithelial-mesenchymal transition, cancer stem cells, epidermal growth factor receptor

Abbreviations: PHS, phytosphingosine; CSC, cancer stem-like cells; EMT, epithelial-mesenchymal transition; EGFR, epidermal growth factor receptor

Received: July 12, 2017    Accepted: August 04, 2017    Published: September 08, 2017

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, 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.


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