CRYAB在热休克因子HSF1诱导CAFs激活促进卵巢癌转移中的功能研究

广泛转移是卵巢癌瘤体减灭不彻底、高复发高死亡率的直接原因。我们对癌相关成纤维细胞（CAFs）促卵巢癌细胞迁移浸润作用进行检测，结果提示作为不同侵袭潜能代表的I型和Ⅱ型卵巢癌（EOC）组织内的CAFs对肿瘤细胞迁移浸润的促进潜能也不同，故推测促使间质内成纤维细胞(NFs)活化为CAFs的能力与癌细胞本身相关，而机制有待阐明：活化热休克因子1（HSF1）在I型和Ⅱ型EOC 肿瘤间质内的差异表达支持其参与了CAFs的激活，但直接途径不明：依据生物信息分析和预实验结果，提出并证明HSF1可能是通过其下游靶基因CRYAB，激活TGF-β1/smad4通路，促进卵巢癌细胞外基质的产生及重塑，活化CAFs，从而反过来成为癌细胞侵袭迁移的助推手，该结果可能为正确理解肿瘤微环境在卵巢癌进展及治疗中的意义提供理论依据。

Wide spread metastasis accounts for the impossibility of complete resection and thus the high recurrence and death rate of epithelial ovarian cancer(EOC). Given the role of cancer associated fibroblasts ( CAFs )in promoting the migration and invasiveness of cancer cells, the function of CAFs in ovarian cancer tissues was evaluated: Both cancer cells and CAFs from type II EOC demonstrated higher migration and invasiveness than those from type I EOC. Moreover, CAFs from type II EOC displayed higher ability of promoting the migration of cancer cells. All the results support that the function of CAFs was based on the action of cancer cells..Activated heat shock factor 1( HSF1)was reported to be associated with CAFs activation. The differential expression of active HSF1 in the stroma of type II EOC from that of type I EOC support its involvement in CAFs activation. To explore the possible pathway, CRYAB was supposed to be the downstream target of HSF1 based on gene ontology enrichment analysis. The project is to propose and to testify whether NFs is induced as CAFs by HSF1, which targets its downstream molecule αB-crystallin and activate TGF-β1/smad4 pathway.