SREBP1 promotes the invasion of colorectal cancer accompanied upregulation of MMP7 expression and NF-κB pathway activation.
BACKGROUND
Sterol-regulatory element binding protein 1 (SREBP1), an intracellular cholesterol sensor located in the endoplasmic reticulum, regulates the intracellular cholesterol by the Insig-Srebp-Scap pathway. Over-expression of SREBP1 can cause dyslipidemia. SREBP1 can regulate the metabolic pathway, and then promote the proliferation of tumor cells. However, there is no relevant research of metastasis and invasion in the field of colorectal cancer (CRC).


METHODS
Expression of SREBP1 was manipulated in CRC cell lines with low and high level SREBP1 expression by transfectiong with plasmids containing the SREBP1 gene, or by shRNA. The effect of SREBP1 on cell migration was assayed. The expression of SREBP1, p65 and MMP7 were detected by western blot. Human umbilical vein endothelial cell was used for detection of angiogenesis by adding the culture supernatant from HT29 and SW620. The level of reactive oxygen species (ROS) was detected by Dihydroethidium (DHE) staining. NF-κB inhibitor SN50 was used to test the relationship of SREBP1, NF-κB pathway and MMP7.


RESULTS
We found that the expression of SREBP1 in colon adenocarcinoma was significantly higher than that in noncancerous tissues, especially in the invasive tumor front including tumor budding. In vitro, SREBP1 over-expressed in colon cancer cell lines HT29 promoted angiogenesis in endothelial cells, increased ROS levels, phosphorylation of NF-κB-p65 and increases MMP7 expression. The effect of SREBP1 on expression of MMP7 was lost following treatment with the NF-κB inhibitor SN50.


CONCLUSION
Our results suggest that SREBP1 can promote the invasion and metastasis of CRC cells by means of promoting the expression of MMP7 related to phosphorylation of p65.
['Gao|Yuyan|Y|http://orcid.org/0000-0003-4765-4477', 'Nan|Xianxiu|X|', 'Shi|Xinjue|X|', 'Mu|Xiaoqin|X|', 'Liu|Binbin|B|', 'Zhu|Huifen|H|', 'Yao|Bingqing|B|', 'Liu|Xinyi|X|', 'Yang|Tianyue|T|', 'Hu|Yiting|Y|', 'Liu|Shulin|S|']
D000328:Adult D000368:Aged D045744:Cell Line, Tumor D002465:Cell Movement D015179:Colorectal Neoplasms D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D020783:Matrix Metalloproteinase 7 D008875:Middle Aged D016328:NF-kappa B D060787:Neoplasm Grading D009367:Neoplasm Staging D009389:Neovascularization, Pathologic D010766:Phosphorylation D017382:Reactive Oxygen Species D015398:Signal Transduction D051780:Sterol Regulatory Element Binding Protein 1
SREBP1 Invasion MMP7 NF-κB CRC