SPHK1 regulates proliferation and survival responses in triplenegative breast cancer
MetadataShow full item record
This article is published under the Open Access publishing model and distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/. Please refer to the licence to obtain terms for any further reuse or distribution of this work.
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.
Showing items related by title, author, creator and subject.
Quality of life in women during and after treatment for breast cancer: a systematic review of qualitative evidenceDevi, M.; Hegney, Desley (2011)Background: Breast cancer is the most common cancer in women. With increasing numbers of women surviving breast cancer, there is a need to move beyond the traditional ways of evaluating clinical outcomes and include ...
Thomson, Allyson; Heyworth, J.; Girschik, J.; Slevin, Terry; Saunders, C.; Fritschi, Lin (2014)Background: Attributions of causality are common for many diseases, including breast cancer. The risk of developing breast cancer can be reduced by modifications to lifestyle and behaviours to minimise exposure to specific ...
Lizama, N.; Rogers, P.; Thomson, Allyson; Slevin, Terry; Fritschi, L.; Saunders, C.; Heyworth, J. (2015)Objective: Our study sought to ascertain women's beliefs about breast cancer risk factors and whether these beliefs differed by demographic factors and personal and family history of breast cancer. Methods: Participants ...