Arl13b通过调控Smo和VEGFR2协同促进神经胶质细胞瘤生长的分子机制

神经胶质细胞瘤(简称胶质瘤)是神经系统常见恶性肿瘤，尚无有效治疗方案。Arl13b是细胞表面信号感受器-初级纤毛的重要组成成份。最近我们发现Arl13b既通过与Smo互作调控Hh通路活性又通过与VEGFR2互作调控VEGF通路活性；Arl13b异常高表达促进胶质瘤细胞增殖；Arl13b的表达水平受转录因子ATF1和泛素化酶DZIP3调控。据此假设：异常高表达的Arl13b通过调控Smo和VEGFR2进而激活Hh和VEGF信号通路促进胶质瘤细胞增殖及肿瘤生长。我们制备了2种Arl13b小鼠动物模型，拟用此模型深入研究Arl13b及相关复合体在胶质瘤发病过程中的作用及机制，重点研究Arl13b对VEGF信号通路的调控；揭示Arl13b异常高表达的原因；阐明异常高表达的Arl13b通过调控Hh和VEGF信号通路协同促进胶质瘤细胞增殖和肿瘤生长的分子机制，为胶质瘤的诊断和治疗提供新的靶点。

Glioma is a common malignant tumor of the nervous system. Arl13b is an importantcomponent of primary cilia, which are signal receptors on cell surface. Recently,we found that Arl13b not only regulates the activity of Hh pathway by interacting with Smo, but also regulates the activity of VEGF pathway by interacting with VEGFR2. Abnormal high expression of Arl13b promoted the proliferation of glioma cells. The expression level of Arl13b is regulated by the transcription factor ATF1 and the ubiquitination enzyme DZIP3. It is hypothesized that abnormally high expression of Arl13b promotes glioma cell proliferation and tumor growth by regulating Smo and VEGFR2 and thereby activating Hh and VEGF signaling pathways. We prepared two animal models of Arl13b mice and planned to use this model to further study the role and mechanism of Arl13b and related complexes in the pathogenesis of glioma, focusing on the regulation of Arl13b on VEGF signaling pathway. What's more, we will reveal the reason for the abnormally high expression of Arl13b.This project will clarify the molecular mechanism by which the abnormally high expression of Arl13b synergistically promotes the proliferation and tumor growth of glioma cells by regulating the Hh and VEGF signaling pathways, providing a new target for the diagnosis and treatment of glioma.