癌相关成纤维细胞来源FMN1促进鼻咽癌侵袭转移的分子机制研究

Cancer-associated fibroblasts (CAF) play an important role in the invasion and metastasis of nasopharyngeal carcinoma (NPC), but the role of CAF in promoting the invasion and metastasis of NPC and its molecular mechanism are still unclear. Our previous studies have shown that the number of CAF in NPC tissue is an independent prognostic factor affecting the distant metastasis-free survival of NPC patients, and co-culture of CAF and NPC cell lines can significantly promote the invasion, migration and epithelial mesenchymal transformation (EMT) of of NPC cell lines. The RNA-seq analysis screened FMN1 gene may be the key signal factor to promote these functions. Based on previous literature, we infer that CAF may act on NPC cells by secreting FMN1, activate downstream pathway to promote EMT to regulate invasion and metastasis of NPC. Based on the previous work, this project intends to explore the molecular mechanism of FMN1 regulating invasion and metastasis of NPC through the study of cell biology, molecular biology, metastasis animal models and clinical specimens, so as to provide new clues for the prevention and treatment of NPC metastasis.

癌相关成纤维细胞（CAF）在肿瘤侵袭转移中起着重要作用，而其促进鼻咽癌侵袭转移的作用及分子机制尚不明确，我们前期研究结果表明鼻咽癌组织中CAF数量为影响鼻咽癌患者无远处转移生存的独立预后因素，且CAF与鼻咽癌细胞系共培养能显著地促进鼻咽癌细胞系的侵袭和迁移能力以及发生上皮间充质化（EMT）。转录组基因测序分析筛选到FMN1基因可能为促进该功能的关键信号因子，结合既往文献报道，我们推断CAF可能通过分泌FMN1作用于鼻咽癌细胞，激活下游通路发生EMT调控鼻咽癌的侵袭转移。本项目拟在前期工作基础上通过细胞生物学、分子生物学、转移动物模型及临床标本研究，深入探讨FMN1调控鼻咽癌侵袭转移的分子机制，为鼻咽癌转移的防治提供新的线索。

肿瘤微环境在肿瘤侵袭转移过程中起着重要作用，成纤维细胞及外泌体作为肿瘤微环境重要的组成成分，其促进鼻咽癌侵袭转移的作用及分子机制尚不明确。本研究通过临床样本生存预后分析，细胞实验，动物实验，生物信息学分析等途径，一方面证明了癌相关成纤维细胞分泌的FMN1为促进鼻咽癌侵袭和转移的关键分子，另一方面明确了鼻咽癌患者血浆或鼻咽癌细胞来源的外泌体携带的PD-L1可通过与CD8+ T细胞表面的PD-1相互结合，抑制CD8+ T细胞活性，而促进鼻咽癌免疫逃逸，从而导致鼻咽癌的侵袭转移。本研究为鼻咽癌的治疗提供了新的理论依据和研究靶点。