Itgb4-KO Mouse

Itgb4, also known as integrin beta 4, is a transmembrane protein that functions as a mechanosensor, mediating bidirectional information exchange between the intracellular and extracellular matrices. It plays a crucial role in cell adhesion, migration, and signaling, and is involved in pathways such as those related to focal adhesion kinase (FAK), protein kinase B (AKT), and matrix metalloproteinases (MMPs) [2].

In cancer research, Itgb4-overexpressing triple-negative breast cancer cells can transfer Itgb4 proteins to cancer-associated fibroblasts (CAFs) via exosomes, inducing BNIP3L-dependent mitophagy and lactate production in CAFs, which in turn promotes breast cancer cell proliferation, epithelial-to-mesenchymal transition, and invasion [1]. In liver cancer, PD-L1 forms a complex with EGFR and Itgb4, activating the PI3K/Akt/mTOR/SREBP1c signaling pathway to reprogram lipid metabolism [3]. In lung adenocarcinoma, Itgb4 may be a prognostic biomarker and is correlated with brain metastasis, as its knockdown inhibits the invasion and migration of brain metastasis cells [5]. In esophageal carcinoma, NEDD4L mediates Itgb4 ubiquitination and degradation to suppress tumor progression [7].

In airway-related studies, Itgb4 deficiency in airway epithelial cells enhances asthma susceptibility and airway remodeling through the SHP2/JNK/c-Jun/FGF2 signaling pathway [4]. It also aggravates RSV infection and increases HDM sensitivity by down-regulating IFN-λ through the EGFR/IRF-1 pathway [6], and induces DNA damage by down-regulating HDAC1 under stress stimulation [8]. Additionally, Itgb4 mediates Zika virus attachment and infection, as its knockout hampers ZIKV binding and replication in host cells [9].

Overall, Itgb4 plays diverse and significant roles in multiple biological processes and disease conditions, and gene knockout/conditional knockout mouse models have been valuable in revealing these functions.