CYP2S1 Knockout Promotes Intestinal Tumor Growth in APCMin/+ Mice and Its Clinical Significance

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. Many studies have attempted to elucidate the role of cytochrome 450 (CYP450) polymorphisms in cancer susceptibility and tumor progression. However, the function of Cytochrome P450 Family 2 Subfamily S Member 1(CYP2S1), a member of the CYP450 family, in CRC remains unclear. Here, we constructed APC Min/+;CYP2S1-/- mice. We found that CYP2S1 knockout in APC Min/+ mice led to an increased number of adenomas, accelerated tumor progression and enhanced proliferation and angiogenesis of adenomas. Consistently, in vitro experiments demonstrated that CYP2S1 silencing enhanced the proliferation, migration and invasion of CRC cells. Furthermore, CYP2S1 knockout promoted the nuclear translocation of β-catenin in intestinal epithelial cells of APCMin/+ mice and in cancer cells, it also activated Wnt and modulated P53 signaling pathways, upregulating metastasis associated in colon cancer 1 (MACC1), which accelerated cancer cell proliferation and invasion. Database analysis revealed that CYP2S1 was upregulated in colorectal cancer and positively associated with better prognosis. In conclusion, these findings suggest that CYP2S1 represents a promising biomarker and therapeutic target for improving the prognosis and treatment of colorectal cancer.