Matrix remodeling-associated protein 8 (MXRA8) (MXRA8)

Matrix remodeling-associated protein 8 (MXRA8), also known as Limitrin or DICAM, is a type I transmembrane protein belonging to the immunoglobulin superfamily (UniProt Q9BRK3). It has gained significant attention as a primary entry receptor for multiple arthritogenic alphaviruses, such as Chikungunya, Mayaro, and Ross River viruses, by binding to the viral E2 glycoprotein (Zhang et al., 2019, Nature). In oncology, MXRA8 is frequently overexpressed in the tumor microenvironment and on various tumor cells, including those in gliomas and colorectal cancer, where it facilitates cell migration, invasion, and the epithelial-mesenchymal transition (EMT) (Han et al., 2020). Beyond its role in infection and malignancy, MXRA8 is expressed in the blood-brain barrier (BBB) and plays a role in maintaining vascular integrity and regulating osteoclast differentiation (Jung et al., 2012). Therapeutic development focuses on monoclonal antibodies and soluble MXRA8-Fc fusion proteins to block viral attachment or inhibit tumor progression. However, targeting MXRA8 poses challenges due to its physiological role in the BBB and bone homeostasis, which could lead to off-target effects.

Other names

LimitrinDICAMDual Ig domain-containing adhesion moleculeASP3

Competitive inhibition of viral entry; blockade of tumor cell adhesion and EMT-related signaling pathways.