PODX调控Wnt/β-catenin信号通路对多形性胶质母细胞瘤增殖的影响及其机制研究

Multiforme glioblastoma (GBM) is the most common and malignant primary brain tumor in adults, with lack of effective treatment. Podocalyxin (PODX) and Wnt/β-catenin signaling pathway were found to play an important role in the development and progression of GBM. We first discovered PODX may promote the proliferation of GBM by increasing the levels of β-catenin in previous studies, but the specific mechanism remains to be studied. Dishevelled protein is the key to Wnt signaling pathway, Wnt signaling can pass from the envelope receptor to the downstream effectors. We found PODX formed a complex with Dishevelled in coimmunoprecipitation experiments, suggesting that there may be interactions between them. The project intends to detect PODX expression in clinical samples, verify PODX proliferation of GBM tumor in orthotopic transplantation animal models, and explore the specific mechanism how PODX activate β-catenin signals. We attempt to reveal PODX regulating GBM proliferation and specific mechanisms through Wnt signaling pathway, to provide new ideas and potential therapeutic targets for prevention and treatment.

多形性胶质母细胞瘤（GBM）是成年人中最常见和恶性程度最高的原发性脑肿瘤，且目前缺乏有效的治疗方式。Podocalyxin（PODX）和Wnt/β-catenin信号通路分别被发现在GBM的发生和发展过程中起到了重要作用。申请者在前期研究中首次发现PODX可能通过增加β-catenin水平促进GBM的增殖，然而具体机制尚待研究。Dishevelled（Dvl）是Wnt信号通路上的关键蛋白，能将Wnt信号从包膜受体传递到下游的效应因子上。申请者前期通过免疫共沉淀实验，证实PODX与Dvl之间可能存在相互作用。本项目拟深入探讨PODX通过Dvl激活β-catenin信号的具体机制，并进一步在临床标本中检测PODX的表达，在原位移植动物模型实验中验证PODX对GBM肿瘤增殖的影响。试图首次揭示PODX调控Wnt信号通路对GBM增殖的影响和具体机制，为其防治提供新的思路和潜在的治疗靶点。

多形性胶质母细胞瘤(GBM)是成年人中最常见和恶性程度最高的原发性脑肿瘤，且目前 缺乏有效的治疗方式。Podocalyxin(PODX)和Wnt/β-catenin信号通路分别被发现在GBM的发 生和发展过程中起到了重要作用。申请者在前期研究中首次发现PODX可能通过增加β-catenin 水平促进GBM的增殖，然而具体机制尚待研究。Dishevelled(Dvl)是Wnt信号通路上的关键蛋 白，能将Wnt信号从包膜受体传递到下游的效应因子上。本项目证实 PODX通过Dvl调控Wnt/β-catenin信号传导通路，促进多形性胶质母细胞瘤的增殖。并且进一步在临床标本中检测了PODX的高表达与胶质瘤的恶性程度相关，然后运用移植裸鼠动物模型实验在体内验证了PODX通过Dvl促进了多形性胶质母细胞瘤的生长。为治疗多形性胶质母细胞瘤寻找新的靶点，以及提供更直接的理论和实验依据。

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