SDF-1/CXCR4通过Hippo-YAP信号通路调控皮肤鳞状细胞癌演进的机制研究

皮肤鳞状细胞癌是仅次于基底细胞癌的第二常见的皮肤恶性肿瘤，是非黑素瘤皮肤肿瘤致死的首要原因，其发生发展的精确分子机制尚不明确。研究表明，基质细胞衍生因子（SDF-1）及其受体CXCR4和Hippo信号通路中的YAP在肿瘤的演进过程具有重要的调控作用。我们前期研究表明SDF-1/CXCR4、YAP在皮肤鳞状细胞癌组织及细胞系中高表达。因此，本项目拟通过体内外实验研究SDF-1/CXCR4、YAP蛋白与皮肤鳞状细胞癌细胞的增殖、迁移、侵袭等恶性生物学特征的关系，并深入探讨其分子机制和调控作用；结合皮肤鳞状细胞癌患者临床组织学标本分析SDF-1/CXCR4、YAP蛋白高表达与患者临床病理参数、生存期之间的关系。该研究将揭示SDF-1/CXCR4、Hippo-YAP信号通路在皮肤鳞状细胞癌演进过程中的作用及分子机制，为皮肤鳞状细胞癌的预后评估和侵袭转移控制提供有效靶标。

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin malignancies after cutaneous basal cell carcinoma. Moreover, it is the primary cause of death in non-melanoma skin tumours. However, the exact molecular mechanism of its occurrence and development are still unclear. Recent researches have shown that stromal cell derived factor-1(SDF-1) and its receptors CXCR4, and YAP, which belongs to Hippo signalling pathway, have a significant effect on the regulation of tumour progression. Our previous studies demonstrated that SDF-1/CXCR4 and YAP were highly expressed either in cutaneous squamous cell carcinoma (CSCC) tissues or cell lines. Therefore, we are aimed to investigate the relationship between the SDF-1/CXCR4, YAP protein and malignant biological characteristics such as proliferation, migration and invasion of skin squamous cell carcinoma through functional experiments in vitro and in vivo, and also, explore its molecular mechanism and regulation. and to analyze the relationship among the high expression of SDF-1/CXCR4 and YAP protein, clinicopathological parameters, survival time,in combination with the clinical histological specimens of cutaneous squamous cell carcinoma (CSCC) patients. Based on the previous findings, this study will further reveal the role of SDF-1/CXCR4 and hippocampal YAP signaling pathway, also the involved molecular mechanism in.the evolution of cutaneous squamous cell carcinoma. So that, we will provide an effective target for overcoming the prognosis evaluation, invasion and metastasis of cutaneous squamous cell carcinoma.