SPHK1 regulates proliferation and survival responses in triple-negative breast cancer

被引：67

作者：

Datta, Arpita ^{[1
]}

Loo, Ser Yue ^{[1
,2
,3
,5
]}

Huang, Baohua ^{[1
]}

Wong, Lingkai ^{[6
]}

Tan, Sheryl S. L. ^{[1
]}

Tan, Tuan Zea ^{[5
]}

Lee, Soo-Chin ^{[5
,7
,8
]}

Thiery, Jean Paul ^{[3
,5
,8
,9
]}

Lim, Yaw Chyn ^{[1
,4
]}

Yong, Wei Peng ^{[5
,7
,8
]}

Lam, Yulin ^{[6
]}

Kumar, Alan Prem ^{[2
,5
,8
,10
,11
]}

Yap, Celestial T. ^{[1
,8
]}

机构：

[1] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117548, Singapore

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117548, Singapore

[3] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117548, Singapore

[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pathol, Singapore 117548, Singapore

[5] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore

[6] Natl Univ Singapore, Dept Chem, Singapore 117548, Singapore

[7] Natl Univ Singapore Hosp, Dept Haematol Oncol, Singapore 117548, Singapore

[8] Natl Univ Canc Inst, Singapore, Singapore

[9] ASTAR, IMCB, Singapore, Singapore

[10] Curtin Univ, Fac Hlth Sci, Sch Biomed Sci, Bentley, WA, Australia

[11] Univ N Texas, Dept Biol Sci, Denton, TX 76203 USA

来源：

ONCOTARGET | 2014年 / 5卷 / 15期

基金：

英国医学研究理事会;

关键词：

sphingosine kinase; breast cancer; chemotherapy; ATHYMIC NUDE-MICE; SPHINGOSINE KINASE; FUNCTIONAL-CHARACTERIZATION; SPHINGOLIPID METABOLISM; MOLECULAR-CLONING; CELLS; 1-PHOSPHATE; DOXORUBICIN; EXPRESSION; DOCETAXEL;

D O I：

10.18632/oncotarget.1874

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：5920 / 5933

页数：14

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