目的： 研究纤维连接蛋白Ⅲ型域包含蛋白10 （FNDC10）对乳腺癌细胞增殖、迁移和侵袭等能力的影响，并初步探讨其作用机制。 方法： 采用TCGA数据库分析FNDC10在乳腺癌组织中表达情况。通过qPCR检测FNDC10在正常永生化乳腺细胞（MCF-10A）和乳腺癌细胞（MCF-7、MDA-MB-231、BT549、MDA-MB-468、HCC1806和HCC1937）中的表达水平。选取MCF-7和MDA-MB-231细胞转染FNDC10 siRNA或对照siRNA后进行功能实验：CCK-8实验检测FNDC10对乳腺癌细胞增殖的影响，集落形成实验检测对乳腺癌细胞集落形成能力的影响，Transwell实验检测其对乳腺癌细胞迁移和侵袭能力的影响，WB法检测转移相关分子和细胞信号通路在蛋白水平的变化。 结果： FNDC10在乳腺癌组织中的表达水平明显高于正常组织（P<0.01），FNDC10在乳腺癌细胞MCF-7和MDA-MB-231内表达水平高于正常乳腺细胞（P<0.01或P<0.05）。敲低FNDC10表达抑制了乳腺癌细胞的增殖、迁移和侵袭（P<0.01或P<0.05）。机制研究表明，干扰FNDC10表达抑制了乳腺癌细胞中STAT3的活化（P<0.01或P<0.05），促进了细胞EMT标志物E-cadherin的表达（P<0.05），抑制了EMT进程。 结论： FNDC10通过增强STAT3信号通路活化促进乳腺癌细胞增殖和EMT进程，从而促进乳腺癌恶性进展。

Objective: To investigate the effects of fibronectin Ⅲ domain containing protein 10 (FNDC10) on the proliferation, migration and invasion of breast cancer cells, and to primarily explore the mechanism. Methods: TCGAdatabase was used to analyze the expression of FNDC10 in breast cancer tissues. The mRNAlevel of FNDC10 in normal immortalized breast cells (MCF-10A) and breast cancer cells (MCF-7, MDA-MB-231, BT549, MDA-MB-468, HCC1806, HCC1937) was detected by qPCR. MCF-7 and MDA-MB-231 cells were transfected with FNDC10 siRNA or NC-siRNA for functional experiments. CCK-8 assay was used to detect the effect of FNDC10 on the proliferation of breast cancer cells. Colony forming assay was used to detect the colony forming ability of breast cancer cells. Transwell assay was used to detect the effect of FNDC10 on migration and invasion of breast cancer cells. WB was used to detect the changes of metastasis- related molecules and cell signaling pathways at protein level. Results:The expression of FNDC10 in breast cancer tissues was significantly higher than that in normal tissues (P<0.01), and the expression level of FNDC10 in breast cancer MCF-7 and MDA-MB-231 cells was higher than that in normal breast cells (P<0.01 or P<0.05). Knocking down FNDC10 expression inhibited the proliferation, migration and invasion of breast cancer cells (P<0.01 or P<0.05). The mechanism study showed that knockdown of FNDC10 expression inhibited STAT3 activation in breast cancer cells (P<0.01 or P<0.05) and enhanced the expression of EMT maker E-cadherin (P<0.05), leading to the suppression of EMT progression. Conclusion: FNDC10 promotes proliferation and EMT of breast cancer cells through activating STAT3 signaling pathway, thereby promoting the malignant progression of breast cancer.

R737.9；R730.2

中央高校基本科研业务费项目（No. 3332021075）