NR2F6 enhances glioma invasion and migration through upregulation of COL1A1 and activation of integrin signaling

Glioma represents the most aggressive form of intracranial malignant tumor, characterized by a poor prognosis in affected patients. Nuclear receptor NR2F6 has been implicated as an oncogenic factor in various cancers; however, its specific role and underlying mechanisms in glioma invasion and migration remain poorly understood. This study aims to investigate whether NR2F6 promotes glioma cell invasion and migration in IDH wild-type glioma cells through regulation of the COL1A1-integrin signaling pathway. Bioinformatics analyses were performed using data from The CPTAC databases to assess NR2F6 expression levels and identify associated functional pathways. Clinical glioma tissue samples were collected, and NR2F6 protein expression was validated via immunohistochemistry. In vitro experiments were conducted using human glioma cell lines (U251 and LN229), in which NR2F6 overexpression and knockdown models were established using lentiviral transfection. Western blotting was employed to detect the expression levels of NR2F6, COL1A1, and key components of the integrin pathway, including integrin, phosphorylated FAK (p-FAK) and phosphorylated Src (p-Src). Cell migration and invasion capacities were evaluated using scratch wound healing and Transwell invasion assays. NR2F6 was significantly upregulated in high-grade glioma tissues and cell lines. Bioinformatics analysis revealed that NR2F6 is functionally enriched in extracellular matrix organization and focal adhesion pathways and exhibits a positive correlation with COL1A1 expression. Functional assays demonstrated that NR2F6 overexpression markedly enhanced the migratory and invasive capabilities of IDH wild-type glioma cells, whereas NR2F6 knockdown suppressed these phenotypes. Mechanistically, NR2F6 positively regulates COL1A1 and integrin expression and activates downstream FAK and Src phosphorylation.