CGREF1 promotes cancer cell migration and predicts poor prognosis in colorectal cancer

Cell growth regulator with EF-hand domain 1 (CGREF1) has been implicated in the upregulation across various cancer types. However, its functional role and clinical relevance in colorectal cancer (CRC) remain poorly characterized. The current study explored the role of CGREF1 in the development and progression CRC.

Bioinformatics analysis was used to examine the expression of CGREF1 in various malignancies, including CRC. Immunohistochemistry (IHC) and Quantitative real-time PCR (qRT-PCR) were performed to determine the expression of CGREF1 in CRC tissues. In vitro proliferation and invasion assays, and orthotopic mouse metastatic model were used to analyze the effect of CGREF1 on the development and progression of CRC.

Bioinformatics analyses confirmed significant upregulation of CGREF1 in multiple malignancies, including CRC. qRT-PCR validated these findings by showing a marked increase in CGREF1 mRNA levels in CRC tissues relative to paired normal adjacent tissues. Consistently, IHC evaluations further corroborated these findings, demonstrating that CGREF1 expression was significantly upregulated in human CRC tissues compared to matched adjacent normal intestinal epithelial tissues. Notably, high expression levels of CGREF1 were significantly correlated with aggressive tumor characteristics and poorer prognostic outcomes in CRC patients. Specifically, CGREF1 expression was markedly elevated in high-grade budding (Bd3), highlighting its potential role in this critical process. Knockdown of CGREF1 in CRC cells significantly attenuated the migration capacity in vitro and in vivo, but did not affect cellular proliferation. Furthermore, knockdown of CGREF1 decreased attenuated F-actin polymerization and reduced pseudopodia formation in CRC cells.

Our findings establish CGREF1 as a critical promoter of CRC migration and a potential prognostic biomarker, providing novel insights into the molecular mechanisms underlying CRC metastasis.