头颈部鳞状细胞癌（HNSCC）是全球最常见的癌症之一，有较高的发病率和病死率。局部复发和远处转移是其预后不良的主要原因。现有研究证实细胞外基质的降解异常是导致HNSCC侵袭和转移的重要因素。申请人前期实验发现：HNSCC细胞通过形成伪足小体促进细胞外基质的降解，且与无脑回综合症致病基因(lissencephaly 1，LIS1)和细胞质连接蛋白170（cytoplasmic linker proteins 170, CLIP170）的相互作用及表达上调有关，但具体的作用机制尚不清楚。本课题旨在研究LIS1/CLIP170调控伪足小体形成在HNSCC侵袭和转移过程中的作用，并深入探讨其下游信号分子在上述过程中的具体分子机制；在此基础上以裸鼠HNSCC模型为实验对象，探讨靶向LIS1/CLIP170以抑制肿瘤侵袭和转移在HNSCC治疗中的可行性，为开拓HNSCC靶向治疗新疗法提供理论基础。

Head and neck squamous cell carcinoma is one of the most prevalent cancers in the world, which has a high morbidity and mortality. Local recurrence and distant metastasis is considered to be the main cause of poor prognosis. Previous studies have demonstrated that the cause of invasion and metastasis was associated with the reduced extracellular matrix (ECM) in HNSCC. Moreover, our preliminary researches indicate the formation of invadopodia in HNSCC cells, which may play important roles in the increase of ECM degradation and result from the up-regulation of Lissencephaly 1 (LIS1) and Cytoplasmic linker proteins 170 (CLIP170) protein complex. The aims of our project are as follows: (1) To uncover the roles of LIS1/CLIP170 and invadopodia in the invasion and metastasis of HNSCC; (2) To investigate the effects of related signaling pathway in the above process; (3) To explore the feasibility and validity of LIS1/CLIP170-targeting in treating HNSCC using the murine model. Our research may further unmask the function of invadopodia during the invasion and migration of HNSCC, and would be beneficial for developing novel therapeutic strategies against HNSCC.