Starfish polysaccharides downregulate metastatic activity through the MAPK signaling pathway in MCF-7 human breast cancer cells

2013 ◽  
Vol 40 (10) ◽  
pp. 5959-5966 ◽  
Author(s):  
Kyu-Shik Lee ◽  
Jin-Sun Shin ◽  
Kyung-Soo Nam
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Mapk Signaling ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Metastatic Activity ◽  
Mcf 7

scholarly journals Restoring Endocrine Response in Breast Cancer Cells by Inhibition of the Sphingosine Kinase-1 Signaling Pathway

Endocrinology ◽  
2009 ◽  
Vol 150 (10) ◽  
pp. 4484-4492 ◽  
Author(s):  
Olga Sukocheva ◽  
Lijun Wang ◽  
Emily Verrier ◽  
Mathew A. Vadas ◽  
Pu Xia
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

Abstract We previously demonstrated that sphingosine kinase-1 (SphK1) is an important mediator in the cytoplasmic signaling of estrogens, including Ca2+ mobilization, ERK1/2 activation, and the epidermal growth factor receptor transactivation. Here we report for the first time that SphK1 activity is causally associated with endocrine resistance in MCF-7 human breast cancer cells. Enforced overexpression of human SphK1 in MCF-7 cells resulted in enhanced cell proliferation and resistance to tamoxifen-induced cell growth arrest and apoptosis. Tamoxifen-resistant (TamR) MCF-7 cells selected by prolonged exposure to 4-hydroxytamoxifen, exhibited higher levels in SphK1 expression and activity, compared with the control cells. Inhibition of SphK1 activity by either specific pharmaceutical inhibitors or the dominant-negative mutant SphK1G82D restored the antiproliferative and proapoptotic effects of tamoxifen in the TamR cells. Furthermore, silencing of SphK1, but not SphK2, expression by the specific small interference RNA also restored the tamoxifen responsiveness in the TamR cells. Thus, blockade of the SphK1 signaling pathway may reprogram cellular responsiveness to tamoxifen and abrogate antiestrogen resistance in human breast cancer cells.

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