FOXD4 induces tumor progression in colorectal cancer by regulation of the SNAI3/CDH1 axis

Cancer Biol Ther. 2018;19(11):1065-1071. doi: 10.1080/15384047.2018.1480291. Epub 2018 Sep 25.

Abstract

Colorectal cancer (CRC) is ranked third as the most common malignancy, and it develops into metastasis at a high rate. Importantly, distant metastasis is considered to be a key factor for colorectal therapy. In the present study, we identified FOXD4, a transcription factor belonging to the forkhead/winged helix-box (FOX) family, as a novel biomarker for diagnosis and treatment of patients with CRC. We revealed that FOXD4 was up-regulated in CRC tissues and increased the metastatic ability of CRC cells. Additionally, FOXD4 affected the metastasis of CRC by inducing the epithelial-mesenchymal transition (EMT) process. Furthermore, FOXD4 could directly bind the SNAI3 promoter during EMT in CRC and then facilitate CRC metastasis. In summary, the present research strongly suggests that FOXD4 is a valuable marker for CRC, and that targeting FOXD4 may be a novel strategy for enhancing the treatment outcomes of CRC therapy.

Keywords: CDH1; FOXD4; SNAI3; cancer biology; colorectal cancer; epithelial-mesenchymal transition; metastasis; transcription factor.

Grants and funding

This work was supported by the Natural Science Foundation of Shandong Province [ZR2014HQ071]; National Natural Science Foundation of China (NSFC) [81600441].