RETRACTED: FNDC1 Promotes the Invasiveness of Gastric Cancer via Wnt/β-Catenin Signaling Pathway and Correlates With Peritoneal Metastasis and Prognosis

Abstract

BackgroundGastric cancer (GC) has a high morbidity and mortality rate, with peritoneal metastasis (PM) identified as the main site of metastasis. Our previous study found that FNDC1 has a higher frequency of mutations in patients with PM by high-throughput sequencing assay, suggesting that it may be associated with GC invasion and PM, however the specific mechanism remains unclear.MethodsFirst, the correlation between FNDC1 and PM and prognosis of GC was clarified by bioinformatics and clinicopathological analysis. Next, the effect of FNDC1 expression on the invasion and metastasis ability of GC was investigated in vivo and in vitro. Finally, the signaling pathways involved in the regulation of FNDC1 were explored.ResultsFNDC1 was highly expressed in GC and was associated with PM and poor prognosis. FNDC1 was also associated with epithelial-mesenchymal transition (EMT) in GC cells. Through in vivo and in vitro experiments, it was clarified that knockdown of FNDC1 could inhibit the proliferation, invasion, and migration of GC cells. In addition, it was elucidated that FNDC1 promotes EMT through the Wnt/β-catenin signaling pathway.ConclusionFNDC1 may be associated with the invasion of GC and PM after surgery. FNDC1 was highly expressed in GC tissues and cell lines, while significantly associated with poor DFS and OS in GC patients. Both univariate and multivariate analyses suggested that the expression of FNDC1 was an independent factor for GC. Knockdown of FNDC1 also significantly inhibited the proliferation, migration, and activity of GC cells. FNDC1 may promote EMT in GC cells through the regulation of Wnt/β-catenin signaling pathway. FNDC1 has the potential to be used as a predictor of PM and may also be studied in depth as a therapeutic target for GC, which has potential clinical utility and is worthy of further validation.

LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway

“…It is reported that the exosomes in malignant ascites can promote the EMT of gastric cancer cells and increase the diffusion degree of gastric cancer cells in the abdominal cavity [ 31 ]. Chen et al showed that FNDC1 can be closely related to the peritoneal metastasis of gastric cancer by regulating the EMT pathway of cells [ 32 ]. Moreover, studies have shown that FAK activation is an important upstream protein regulating EMT [ 33 , 34 ].…”

Anoikis-related signature identifies tumor microenvironment landscape and predicts prognosis in colorectal cancer

“…In previous reports, FNDC1 and SFRP4 were closely linked to the development of epithelial-mesenchymal transition (EMT), which represents the ability to acquire migration [22,23]. Further, knockdown of FNDC1 was found to inhibit proliferation, invasion and migration of gastric cancer cells, and by modulating the Wnt/β-catenin signaling pathway, FNDC1 may facilitate the EMT of gastric cancer cells [22]. Not coincidentally, SFRP4 expression was also found to be proportional to tumor invasion in gastric cancer, but the exact mechanism has not been elucidated [23].…”

Loss of MAGEC3 Expression Is Associated with Prognosis in Advanced Ovarian Cancers

“…MAGEC3 also upregulates a stress-related gene, WRNIP1 [27], a DNA replication gene, MCM7 [28], and cancer-related genes, XPO5 [29] and ZSCAN16 [30]. In addition, MAGEC3 downregulates genes that are shown to induce tumor progression, including APLMR [31,32], FBLN5 [33], and FNDC1 [34,35]. Gene set enrichment analysis (GSEA) showed that MAGEC3 significantly enriched E2F targets (NES = 3.63, FDR < 0.001), G2/M checkpoint (NES = 3.20, FDR < 0.001), and DNA repair (NES = 2.28, FDR < 0.001), whereas the epithelial to mesenchymal transition was downregulated (NES = −3.34, FDR < 0.001) (Figure 3B).…”