Sterol regulatory element-binding protein 1 cooperates with c-Myc to promote epithelial-mesenchymal transition in colorectal cancer

Oncol Lett. 2018 Apr;15(4):5959-5965. doi: 10.3892/ol.2018.8058. Epub 2018 Feb 15.

Abstract

Metastasis is the primary cause of mortality in colorectal cancer (CRC), the mechanism of which remains unclear. In the present study, by detecting mRNA expression using a reverse transcription-quantitative polymerase chain reaction (qPCR), it was revealed that sterol regulatory element-binding protein 1 (SREBP1) is highly expressed in CRC. Using a cell wound healing assay and a cell invasion assay, a novel metastasis-promoting role for SREBP1 in CRC was identified. Furthermore, snail family transcriptional repressor 1 (SNAIL) was identified as a key downstream effector of SREBP1 in CRC by the use of small interfering RNA against SNAIL. Additionally, using co-immunoprecipitation and chromatin immunoprecipitation-qPCR assays, it was demonstrated that SREBP1 interacts with c-MYC to enhance the binding of c-MYC to the promoter of the mesenchymal gene, SNAIL, thereby increasing SNAIL expression and accelerating epithelial-mesenchymal transition. These results indicated a novel role for SREBP1 and provide insight into the regulatory mechanisms of the c-Myc oncogene in CRC, which may function as a potential therapeutic target for CRC treatment.

Keywords: SNAIL; c-Myc; colorectal cancer; epithelial-mesenchymal transition; sterol regulatory element-binding protein 1.