Ifitm1-flox Mouse

Ifitm1, short for Interferon (IFN)-induced transmembrane protein 1, is a member of the IFN-induced transmembrane protein family. It plays a crucial role in the innate immune response triggered by viral infection, with functions including conferring cellular resistance to many viruses and being involved in intracellular cholesterol transport [2,6,5]. It is also associated with pathways like the STING-TBK1-IRF3 signaling pathway [3].

In cancer, overexpression of Ifitm1 promotes tumor cell proliferation, invasion, metastasis, angiogenesis, and therapeutic resistance in various tumor types such as gallbladder carcinoma, esophageal adenocarcinoma, colorectal cancer, and gastric cancer, making it an independent prognostic biomarker [1]. In colorectal cancer, Apc mutation induces Ifitm1 expression, and high Ifitm1 levels in cells reduce fibroblast extracellular vesicle (EV) uptake, with functional implications for cell proliferation [4]. In lung adenocarcinoma, high expression of Ifitm1, along with FOXM1 and PLK1, is inversely correlated with patient survival rate, as Ifitm1 enhances FoxM1-mediated signaling [3]. In brain metastasis from lung cancer, loss of Ifitm1 promotes brain colonization, while high Ifitm1 expression in incipient metastatic cells activates microglia and CD8+ T cells to eliminate cancer cells, and it also enhances the efficacy of PD-1 blockade [9].

In viral infections, overexpression of Ifitm1 suppresses porcine epidemic diarrhea virus (PEDV) proliferation [2]. It also enhances non-enveloped viral (Aichi virus) RNA replication by facilitating cholesterol transport to the Golgi [5]. In SARS-CoV-2 infection, IFITM1 methylation is higher in severe and critical patients, potentially suppressing the immune system and promoting viral replication [7], and IFITM1 inhibits Spike-mediated fusion of SARS-CoV-2-infected cells [8].

In conclusion, Ifitm1 has diverse functions in both antiviral immune responses and cancer-related processes. Model-based research, especially in the context of cancer and viral infections, has revealed its significance in promoting or suppressing disease progression, highlighting its potential as a therapeutic target in these disease areas.