Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
Neoplasia. 2018 Oct;20(10):996-1007. doi: 10.1016/j.neo.2018.08.004. Epub 2018 Sep 10.
Forkhead Box F1 (FOXF1) has been recently implicated in cancer progression and metastasis of lung cancer and breast cancer. However, the biological functions and underlying mechanisms of FOXF1 in the regulation of the progression of colorectal cancer (CRC) are largely unknown. We showed that FOXF1 was up-regulated in 93 paraffin-embedded archived human CRC tissue, and both high expression and nuclear location of FOXF1 were significantly associated with the aggressive characteristics and poorer survival of CRC patients. The GSEA analysis showed that the higher level of FOXF1 was positively associated with an enrichment of EMT gene signatures, and exogenous overexpression of FOXF1 induced EMT by transcriptionally activating SNAI1. Exogenous overexpression FOXF1 functionally promoted invasion and metastasis features of CRC cells, and inhibition of SNAI1 attenuates the invasive phenotype and metastatic potential of FOXF1-overexpressing CRC cells. Furthermore, the results of the tissue chip showed that the expression of FOXF1 was positively correlated with SNAI1 in CRC tissues chip. These results suggested that FOXF1 plays a critical role in CRC metastasis by inducing EMT via transcriptional activation of SNAI1, highlighting a potential new therapeutic strategy for CRC.
叉头框蛋白 F1（FOXF1）最近被牵涉到肺癌和乳腺癌的癌症进展和转移中。然而，FOXF1 在调控结直肠癌（CRC）进展中的生物学功能和潜在机制在很大程度上仍是未知的。我们发现 FOXF1 在 93 例石蜡包埋的存档人 CRC 组织中上调，FOXF1 的高表达和核定位与 CRC 患者侵袭性特征和较差的生存显著相关。GSEA 分析显示，FOXF1 水平越高与 EMT 基因特征的富集呈正相关，外源性过表达 FOXF1 通过转录激活 SNAI1 诱导 EMT。外源性过表达 FOXF1 可功能性地促进 CRC 细胞的侵袭和转移特征，而 SNAI1 的抑制可减弱 FOXF1 过表达 CRC 细胞的侵袭表型和转移潜能。此外，组织芯片的结果显示 FOXF1 在 CRC 组织芯片中的表达与 SNAI1 呈正相关。这些结果表明，FOXF1 通过转录激活 SNAI1 诱导 EMT 在 CRC 转移中发挥关键作用，突出了 CRC 的一种潜在新治疗策略。
