LRIG proteins in glioma: Functional roles, molecular mechanisms, and potential clinical implications.

Gliomas are the most common intracranial tumors of the nervous system. These tumors are characterized by unlimited cell proliferation and excessive invasiveness. Despite the advances in diagnostic imaging, microneurosurgical techniques, radiation therapy, and chemotherapy, significant increases in the progression free survival of glioma patients have not been achieved. Improvements in our understanding of the molecular subtypes of gliomas and the underlying alterations in specific signaling pathways may impact both the diagnosis and the treatment strategies for patients with gliomas. Growth factors and their corresponding receptor tyrosine kinases are associated with oncogenesis and development of tumors in numerous human cancer types, including glioma. Leucine-rich repeats and immunoglobulin-like domains (LRIG) are integral membrane proteins which contain three vertebrate members including LRIG1, LRIG2 and LRIG3. They mainly function as regulators of growth factor signaling. Specifically, LRIG1 has been identified as a tumor suppressor in human cancers. In contrast, LRIG2 appears to function as a tumor promoter, while LRIG3 appears to have a function similar to that of LRIG1. In the present review, we summarize the functional roles, molecular mechanisms, and clinical perspectives of LRIG proteins in gliomas and propose that these proteins may be useful in the future as targets for treatment and prognostication in glioma patients.