Anti-Axl polyclonal antibody [Biotin]

The mumps virus (MuV) causes epidemic parotitis. MuV also frequently infects the testis and induces orchitis, an important etiological factor contributing to male infertility. However, mechanisms underlying MuV infection of the testis remain unknown. Here, we describe that sialic acid, AXL, and MER receptor tyrosine kinases regulate MuV entry and replication in mouse major testicular cells, including Sertoli and Leydig cells. Sialic acid, AXL, and MER were present in Sertoli and Leydig cells. Sialic acid specifically mediated MuV entry into Sertoli and Leydig cells, whereas both AXL and MER facilitated MuV replication within cells through the inhibition of cellular innate antiviral responses. Mechanistically, the inhibition of type 1 interferon signaling by AXL and MER is essential for MuV replication in Sertoli and Leydig cells. Our findings provide novel insights into the mechanisms behind MuV infection and replication in the testis.

AXL belongs to the TAM (TYRO3, AXL, and MERTK) receptor family, a unique subfamily of the receptor tyrosine kinases. Their common ligand is growth arrest-specific protein 6 (GAS6). The GAS6/TAM signaling pathway regulates many important cell processes and plays an essential role in immunity, hemostasis, and erythropoiesis. In cancer, AXL overexpression and activation has been associated with cell proliferation, chemotherapy resistance, tumor angiogenesis, invasion, and metastasis; and has been correlated with a poor prognosis. In hematological malignancies, the expression and function of AXL is highly diverse, not only between the different tumor types but also in the surrounding tumor microenvironment. Most research and clinical evidence has been provided for AXL inhibitors in acute myeloid leukemia. However, recent studies also revealed an important role of AXL in lymphoid leukemia, lymphoma, and multiple myeloma. In this review, we summarize the basic functions of AXL in various cell types and the role of AXL in different hematological cancers, with a focus on AXL in the dormancy of multiple myeloma. In addition, we provide an update on the most promising AXL inhibitors currently in preclinical/clinical evaluation and discuss future perspectives in this emerging field.