The pivotal role of SCD1 in digestive cancers: Bridging lipid metabolic reprogramming and programmed cell death (Review)
TL;DR
This review systematically examined how SCD1 governs three key forms of regulated cell death - ferroptosis, autophagy and apoptosis - thereby driving malignant progression and mediating therapy resistance in digestive cancers.
Abstract
Stearoyl-CoA desaturase-1 (SCD1) has emerged as a critical nexus linking lipid metabolic reprogramming to the regulation of cell death. Frequently overexpressed in digestive system malignancies - including gastric, liver and colorectal cancers - SCD1 represents a promising therapeutic target. This review systematically examined how SCD1, through its lipid-modifying functions, governs three key forms of regulated cell death - ferroptosis, autophagy and apoptosis - thereby driving malignant progression and mediating therapy resistance in digestive cancers. Building on this mechanistic framework, the specific contributions of these regulatory pathways to tumor biology and their association with drug resistance were delineated. Current preclinical therapeutic strategies targeting SCD1 were then highlighted, encompassing both monotherapy and combination approaches with ferroptosis inducers, chemotherapeutic agents or targeted drugs. Finally, key challenges and outline future directions for drug development and clinical translation in this rapidly evolving field were discussed.