FOXF1 Induces Epithelial-Mesenchymal Transition in Colorectal Cancer Metastasis by Transcriptionally Activating SNAI1

Abstract

Forkhead Box F1 (FOXF1) has been recently implicated in cancer progression and metastasis of lung cancer and breast cancer. However, the biological functions and underlying mechanisms of FOXF1 in the regulation of the progression of colorectal cancer (CRC) are largely unknown. We showed that FOXF1 was up-regulated in 93 paraffin-embedded archived human CRC tissue, and both high expression and nuclear location of FOXF1 were significantly associated with the aggressive characteristics and poorer survival of CRC patients. The GSEA analysis showed that the higher level of FOXF1 was positively associated with an enrichment of EMT gene signatures, and exogenous overexpression of FOXF1 induced EMT by transcriptionally activating SNAI1. Exogenous overexpression FOXF1 functionally promoted invasion and metastasis features of CRC cells, and inhibition of SNAI1 attenuates the invasive phenotype and metastatic potential of FOXF1-overexpressing CRC cells. Furthermore, the results of the tissue chip showed that the expression of FOXF1 was positively correlated with SNAI1 in CRC tissues chip. These results suggested that FOXF1 plays a critical role in CRC metastasis by inducing EMT via transcriptional activation of SNAI1, highlighting a potential new therapeutic strategy for CRC.

Identification of new hypoxia‐regulated epithelial‐mesenchymal transition marker genes labeled by H3K4 acetylation

“…New EMT marker genes that are labeled by H3K4Ac and regulated by HDAC3 are identified, including FOXF1 , SIRT2 , GLI1 , SMO , BMI1 , and so forth. FOXF1 has been recently implicated in cancer progression and metastasis of breast cancer, lung cancer, and colorectal cancer, by inducing EMT through upregulating lysyl oxidase and suppressing Smad2/3 signaling, or through transcriptionally activating SNAI1 . The role of SIRT2 in regulating the Akt/GSK‐3β/β‐catenin pathway to mediate EMT and predict prognosis in hepatocellular carcinoma and esophageal squamous cell carcinoma has also been reported.…”

“…GLI1 and SMO expression in HNSCC patients and their relation to clinicopathological factors Estimated by χ 2 or Fisher's exact test (if expected count was less than 5). or through transcriptionally activating SNAI1 40. The role of SIRT2 in regulating the Akt/GSK-3β/β-catenin pathway to mediate EMT and predict prognosis in hepatocellular carcinoma41 and esophageal squamous cell carcinoma42 has also been reported.…”

Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation

“…Western blot was performed according to standard methods as described previously [34]. Anti-Siah1 (Abcam, #ab69638, dilutions: 1:200), anti-phospho-AKT (Cell Signaling Technology, #C31E5E, dilutions: 1:200), anti-AKT (Cell Signaling Technology, #11E7, dilutions: 1:1000), anti-JNK (Bioworld Technology Inc., #BS1544, dilutions: 1:200), anti-phospho-JNK (Bioworld Technology Inc., #BS4322, dilutions: 1:1000), and anti-YAP (Cell Signaling Technology, #8418, dilutions: 1:200) antibodies were used for Western blot.…”

Systematic Expression Analysis of Zinc-finger Transcription Factor Family Reveals the Importance of Snai1 in Colorectal Carcinogenesis

“…Additionally, SNAI1 has been reported to directly or indirectly inhibit the activity of p53, one of the most important anti-oncogene during carcinogenesis [14]. Previous studies have reported that high expression of SNAI1 was signi cantly correlated with tumor metastasis, recurrence and worse prognosis in multiple types of malignancies, including CRC [15], lung cancer [16], breast cancer [17], and ovarian cancer [18]. However, the role of SNAI1 in the carcinogenesis and metastasis of CRC cells remains largely unclear and deserves more attention.…”