title: SPHK1 regulates proliferation and survival responses in triple-negative breast cancer.
abstract: Triple-negative breast cancer (TNBC) is characterized by unique aggressive behavior and lack of targeted therapies. Among the various molecular subtypes of breast cancer, it was observed that TNBCs express elevated levels of sphingosine kinase 1 (SPHK1) compared to other breast tumor subtypes. High levels of SPHK1 gene expression correlated with poor overall and progression- free survival, as well as poor response to Doxorubicin-based treatment. Inhibition of SPHK1 was found to attenuate ERK1/2 and AKT signaling and reduce growth of TNBC cells in vitro and in a xenograft SCID mouse model. Moreover, SPHK1 inhibition by siRNA knockdown or treatment with SKI-5C sensitizes TNBCs to chemotherapeutic drugs. Our findings suggest that SPHK1 inhibition, which effectively counteracts oncogenic signaling through ERK1/2 and AKT pathways, is a potentially important anti-tumor strategy in TNBC. A combination of SPHK1 inhibitors with chemotherapeutic agents may be effective against this aggressive subtype of breast cancer.
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore.
authors.forename: Arpita
authors.initials: A
authors.lastname: Datta
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore; Cancer Science Institute of Singapore, National University of Singapore.
authors.forename: Ser Yue
authors.initials: SY
authors.lastname: Loo
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore.
authors.forename: Baohua
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Chemistry, National University of Singapore, Singapore.
authors.forename: Lingkai
authors.initials: L
authors.lastname: Wong
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore.
authors.forename: Sheryl S L
authors.initials: SS
authors.lastname: Tan
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore.
authors.forename: Tuan Zea
authors.initials: TZ
authors.lastname: Tan
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore; Department of Haematology-Oncology, National University Hospital, Singapore; National University Cancer Institute, Singapore.
authors.forename: Soo-Chin
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore; Cancer Science Institute of Singapore, National University of Singapore; National University Cancer Institute, Singapore; Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Thiery
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore; Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore.
authors.forename: Yaw Chyn
authors.initials: YC
authors.lastname: Lim
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore; Department of Haematology-Oncology, National University Hospital, Singapore; National University Cancer Institute, Singapore.
authors.forename: Wei Peng
authors.initials: WP
authors.lastname: Yong
authors.affiliation: Department of Chemistry, National University of Singapore, Singapore.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Lam
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore; Cancer Science Institute of Singapore, National University of Singapore; National University Cancer Institute, Singapore; School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Western Australia; Department of Biological Sciences, University of North Texas, Denton, Texas, USA.
authors.forename: Alan Prem
authors.initials: AP
authors.lastname: Kumar
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore; National University Cancer Institute, Singapore.
authors.forename: Celestial T
authors.initials: CT
authors.lastname: Yap
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016513:Mice, SCID; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D014162:Transfection; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D000099157:Sphingosine Kinase
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase