Is there an association between S1P signaling and the transcription factor Nrf2?

Nuclear factor-erythroid 2 [NF-E2]-related factor 2 (Nrf2) is a transcriptional activator that can offer protection to cells. By activating cytoprotective genes, Nrf2 can help cells to defend against DNA damage, electrophilic and oxidative stress. However, Nrf2 can also act as an oncogene. The upstream mutation leads to the Nrf2 overexpression and accumulation in the nucleus. In cancer development, overexpressed Nrf2 enhances the resistance of cancers to drugs, chemotherapy or radiotherapy. Sphingosine 1-phosphate is a biological lipid mediator that serves a pivotal function in physiological functions and pathophysiological conditions. Synthesized by sphingosine kinase, S1P regulates several cellular events through five sphingosine 1-phosphate receptors. S1P has been associated with poor prognosis in cancer, metastasis and chemotherapeutic resistance. Dysregulated Nrf2 and S1P are able to enhance chemotherapeutic resistance in cancer development. However, a direct association between Nrf2 and S1P has not been observed yet. The aim of this project was to examine whether there is a relationship between Nrf2 and S1P. Three cancer cell lines were employed and tested for the ability of S1P or sphingosine kinase inhibitors or short-chain ceramides to affect Nrf2. Although the work presented here does not support a relationship between Nrf2 and S1P, a direct connection between these two factors cannot yet be discounted. Based on their roles in cancer development, clarification of the potential connection between Nrf2 and S1P should be investigated further.

Name dc:type.qualificationname

mres

Level dc:type.qualificationlevel

masters-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2016

Author dc:creator

• Huang, Shih-Han

DOI

10.48730/tec3-rn28

Identifier

T14327

Author Identifier

201474657

OAI identifier oai:identifier

oai:strathclyde:pc289j114