FDFT1 (Farnesyl-Diphosphate Farnesyltransferase 1)

Through RNA-seq data and body weight changes in DAPL1 KO mice, we report that DAPL1 regulates cholesterol, PC, and SM through changes in mRNA of Fdft1, Pcyt1a, and Sptlc1. Our data show that Np63, GRα monomer transcription factors activate DAPL1, and it is predicted to regulate lipid metabolism based on mRNA-seq data and DAPL1 KO mice.

This study established an integrated model "multicomponents-multitargets-multiactivities" and offered a theoretical framework to elucidate its molecular mechanisms of antitumor and alleviating chemotherapy-induced toxicities in CRC patients.

The results of this study indicate that the reduction in cholesterol levels observed in breast cancer cells following IGFBP6 knockdown is primarily due to decreased exogenous uptake. These findings highlight the role of IGFBP6 in regulating cholesterol metabolism and further explain its clinical significance in predicting breast cancer recurrence and progression.

The downregulation of FDFT1 by HIV-1 Tat modulates cellular cholesterol levels and is associated with KSHV replication in BCBL-1 cells.

Collectively, our findings shed a new insight that EMC2 is critical for boosting cholesterol biosynthesis and ferroptosis resistance. Targeting EMC2 could be a promising novel therapeutic target for TNBC treatment.

Subsequently, we found that NeuroD1/FDFT1-mediated cholesterol biosynthesis is critical to the tumorigenic potential of HCC cells. These findings not only identify NeuroD1 as a regulator of lipid metabolism in tumor cells, but also reveal a novel molecular mechanism underlying its carcinogenic function.

Co-immunoprecipitation confirmed the interaction between SQLE and farnesyl-diphosphate farnesyltransferase 1 (FDFT1), another rate-limiting enzyme in cholesterol metabolism. These findings suggest that 20(S)-Rg3 exerts anti-ovarian cancer effects by HIF-1α/SQLE/FDFT1 to reprogram cholesterol metabolism.

Our findings suggest that THEM6 enhances carboplatin sensitivity in TNBC by promoting ferroptosis through regulation of FDFT1. THEM6 may serve as a novel therapeutic target to improve TNBC treatment outcomes.

These findings identify Lycorine Hydrochloride as a promising treatment alternative for ICC and propose a novel combination strategy (LY + GEM) for treating multiple solid tumors.

To explore the impact of VPA in combination with ferrostatin-1, Erastin or RSL3, on MDA-MB-231 cell proliferation and ferroptosis, respective CCK-8, colony formation and WB assays were conducted. Additionally, we discovered that VPA may facilitate ferroptosis in MDA-MB-231 cells by negatively modulating the levels of the solute carrier family 7 member 11 (SLC7A11) protein through the upregulation of FDFT1 expression. In conclusion, this study elucidated that VPA induced the ferroptosis of MDA-MB-231 cells via targeting FDFT1, representing a novel mechanism underlying its efficacy in potentially inhibiting breast cancer.

In addition, the expressions of CDKN1A, EMC2, FDFT1, and HSPB1 were associated with the prognosis of multiple cancers (P<0.05). The five ferroptosis-related genes CDKN1A, EMC2, FDFT1, HSPB1, and MT1G exhibited excellent predictive effects for the diagnosis of FA.