LEF1 Suppresses Ferroptosis in Colorectal Cancer Cells by Targeted Promotion of SLC7A11 Transcription

Ferroptosis has emerged as a promising therapeutic target for colorectal Cancer (CRC) due to its ability to selectively eliminate Cancer cells. By inducing Ferroptosis, novel treatment strategies aim to overcome traditional challenges such as Cancer recurrence and drug resistance. In this study, we screened cells with high LEF1 expression, knocked down LEF1, or simultaneously overexpressed SLC7A11 in these cells, and intervened with Ferroptosis inducers and inhibitors to investigate the mechanism of LEF1 in inhibiting Ferroptosis and promoting CRC cell growth. Dual-luciferase reporter assays and CHIP-qPCR were utilized to validate the effect of LEF1 on SLC7A11 transcription. Furthermore, a nude mouse subcutaneous xenograft model was established using CRC cells with stable LEF1 knockdown to verify the impact of LEF1 on CRC tumor growth in vivo. Our findings indicate that LEF1 knockdown inhibits CRC cell progression both in vitro and in vivo. Moreover, we discovered that the molecular mechanism underlying the role of LEF1 is the targeted activation of SLC7A11 transcription, which alleviates Ferroptosis, ultimately leading to CRC progression. Our results suggest that LEF1 inhibits Ferroptosis in CRC cells by promoting SLC7A11 transcription, potentially serving as a therapeutic target for CRC. This study reveals that the promotion of CRC by LEF1 is associated with activating SLC7A11 transcription and inhibiting cellular Ferroptosis, providing a new direction for clinical targeted therapy of CRC.

LEF1; SLC7A11; colorectal cancer; erastin; ferroptosis.