P02.14.A KDELR2 INTERACTS WITH GΑQ REGULATING VASCULOGENIC MIMICRY FORMATION OF GLIOMA VIA SRC/PI3K/MMP2/9 PATHWAY

Abstract BACKGROUND Gliomas are highly vascularized tumors, yet the existing anti-angiogenic therapy is not satisfactory, suggesting the deficiency of interfering classical tumor angiogenic pathways. Our previous work identified the presence of vasculogenic mimicry (VM) composed of tumor cells in glioma that plays an important role in anti-angiogenic therapy resistance. To date, the mechanism of VM is not fully elucidated. In this study, we aimed to investigate the role and mechanism of KDELR2 in VM formation in glioma, and tried to find a useful target for designing more effective approaches to overcome anti-angiogenic therapy resistance. MATERIAL AND METHODS In this study, IHC and transcriptome RNA sequencing of clinical specimens were used for screening out KDELR2 which was responsible for VM formation in glioma. Subsequently, three-dimensional culture, co-immunoprecipitation, immunocytochemistry and western blot were used to confirm the role and the mechanism of KDELR2 in VM formation in vitro and in vivo. RESULTS Our study revealed that KDELR2, a key gene mediating endoplasmic reticulum-Golgi protein transport, was highly expressed in gliomas and functioned as a crucial regulator in VM formation via Src/PI3K/MMP2/MMP9 pathway by coupling and activating Gαq in glioma. CONCLUSION Our results demonstrated that KDELR2 promoted VM formation in glioma by upregulating Src/PI3K/MMP2/9 pathway via activating Gαq, and KDELR2 may be a useful target for designing more effective approaches to treat glioma.