锌指蛋白32调控上皮-间质转化以及肿瘤相关成纤维细胞活化在乳腺癌转移中作用机制的研究

乳腺癌是严重危害女性健康的恶性肿瘤之一，乳腺癌细胞发生转移是患者死亡的主要因素，其转移机制涉及肿瘤细胞自身生物学行为改变及其与微环境之间的相互作用。锌指蛋白（ZNF）32功能不甚清楚，目前仅有我们课题组对其功能进行部分报道。我们前期发现ZNF32在发生转移患者乳腺癌组织和淋巴结转移灶中的表达低于无转移患者乳腺癌组织，并且过表达ZNF32能抑制乳腺癌细胞发生上皮-间质转化（EMT）、体内转移以及肿瘤相关成纤维细胞（CAFs）的活化。本课题拟在前期工作基础上，从ZNF32调控乳腺癌细胞自身EMT发生和与肿瘤微环境中CAFs相互作用的双重角度，阐明ZNF32在乳腺癌细胞转移中的作用及机制，并扩大临床组织样本分析ZNF32及其效应分子与EMT相关蛋白、CAFs标志物、乳腺癌转移、复发和患者生存预后的相关性，明确ZNF32作为乳腺癌预后标志物和基因治疗的潜在应用价值。

Breast cancer is one of the most common cancer among female population worldwide. Metastasis accounts for the major cause of breast cancer related death. Both the intrinsic and extrinsic signal crosstalks are involved in breast cancer metastasis. The functions and regulation of a novel Zinc finger protein 32(ZNF32) has not been known well. We found that ZNF32 expression in tumor tissues from the patients with metastatic breast cancer is much lower compared with those without metastasis. We also demonstrated that both the tumor formation and epithelial to mesenchymal transition (EMT) and processes were attenuated by ZNF32 overexpression in vivo. Additionally, in this context, the activation of cancer associated fibroblasts (CAFs) within the microenvironment was largely inhibited. In this project, we aim to further investigate the molecular mechanism underlying ZNF32-regulated EMT and the exact role of the interaction between tumor cells and CAFs in breast cancer metastasis. Furthermore, the correlations of ZNF32 expression with EMT, CAFs activation and metastasis will be examined in large clinical cohorts. Our study will clarify the significant roles of ZNF32 in breast cancer metastasis which might facilitate the future investigations of ZNF32 in cancer prognosis and gene therapies.