Interferon-induced transmembrane protein 2 promotes epithelial-mesenchymal transition by activating transforming growth factor-β1/small mother against decapentaplegic 2 signaling in gastric cancer

Abstract

Background Gastric cancer (GC) is one of the most prevalent malignancy around the world. Primary tumor cells are enabled to invade and migrate into adjacent normal tissues to form secondary tumors. Epithelial-mesenchymal transitions (EMT) plays a pivotal role in facilitating tumor progression. Abundant evidence suggested that the transforming growth factor-β1 (TGF-β1) triggered the process of EMT. Nonetheless, the precise molecular mechanisms underlying EMT requires further elucidation, and there still lacks effective specific therapeutic target. In our recent research, we demonstrated that the interferon (IFN)-induced transmembrane protein 2 (IFITM2) promoted the growth and metastasis of GC. However, it remains unclear whether IFITM2 involves in TGF-β1 mediated EMT in GC. Methods and resultsIn the present research, we investigated the functional role of IFITM2 in EMT process and TGF-β1 signaling pathway in two GC cell lines. We noticed that silencing IFITM2 can effectively inhibit TGF-β1 signaling mediated EMT by regulating down stream small mother against decapentaplegic (SMAD) 2/3 and transcription factors.This finding was further determined in both tumor tissues from GC patients and normal tissues adjacent to cancer. Our data demonstrated the key role of IFITM2 in TGF-β1 signaling and EMT in GC. ConclusionThe findings enriched our understanding of the underlying mechanism in EMT during the progression of GC. In addition, IFITM2 would be a potential target for treating GC and other malignant tumors. KeywordsCancer invasion and metastasis • Epithelial-mesenchymal transitions • Gastric cancer • IFITM2 • Molecular mechanism • TGF-β1 Abbreviations EMT Epithelial-mesenchymal transitions ECM Extracellular matrix GC Gastric cancer GSEA Gene set enrichment analysis IFITM2 Interferon (IFN)-induced transmembrane protein 2 NES Normalized enrichment score SMAD Small mother against decapentaplegic TGF-β1 Transforming growth factor-β1 ZEB1Zinc finger E-box-binding homeobox 1Yonggang Liu and Minyu Zhou-co-first author.

High expression of IFITM2 in gastric cancer is related to poor prognosis

“…KEGG analysis revealed that IFITM2 was over-expressed in the Antigen processing and presentation, Cytokine and cytokine receptor interaction, Chemokine signaling pathway, Cell adhesion molecules, JAK-STAT signaling pathway and TGF-beta signaling pathway. In our previous study found that IFITM2 was the main component of TGF-β1 pathway that modulates EMT progression in GC (Liu et al, 2022). It has been previously reported that IFITM2 upregulation is associated with cytokine and cytokine receptor interaction functional pathways, and that IFITM2 is positively associated with VEGF-C expression and lymph node metastasis in renal cancer (Yang et al, 2021).…”

“…Recently, overexpression of IFITM2 has been found in colon carcinoma, renal clear cell carcinoma and osteosarcoma (Salas et al, 2009). Our previous study has demonstrated that the effect of IFITM2 on epithelial-mesenchymal transition in GC by activating TGF-β1 pathway (Liu et al, 2022). However, IFITM2 expression and its speci c mechanisms in GC remain unclari ed.…”

IFITM2 is a prognostic in colorectal cancer and promotes progression by activating PI3K/AKT pathway

“…Yang et al found that IFITM2 has a high expression status in renal clear cell carcinoma tissues and cells, and can lead to tumor invasion and metastasis by promoting lymphangiogenesis [24] . Our previous study has demonstrated that the effect of IFITM2 on epithelial-mesenchymal transition in gastric cancer by activating TGF-β1 pathway [25] . However, IFITM2 expression and its speci c mechanisms in CRC remain unclari ed.…”

“…IFITM2 is a potential biomarker in some cancers, but its functional mechanism is still elusive [24][25][26] . In this study, we demonstrated that interfering with IFITM2 expression inhibited the proliferative potential of colorectal cancer cells.…”

“…The occurrence and development of tumors are closely related to the changes of signal pathways. Our previous study has demonstrated that the effect of IFITM2 on epithelial-mesenchymal transition in GC by activating IGF1/IGF1R/STAT3 and TGF-β1/Smad2 pathways [25,26] . Nonetheless, whether IFITM2 in uences CRC development through in ammation has not been investigated.…”