The Dual Role of SLC7A11 in Colorectal Cancer Ferroptosis: From Molecular Mechanisms to Therapeutic Opportunities

Colorectal cancer (CRC) ranks as the third most prevalent malignancy globally based on recent epidemiological studies. In China, the rising incidence and mortality rates of CRC have underscored the importance of elucidating its pathogenic mechanisms, which remain major focus in current biomedical research. Ferroptosis, a regulated cell death process driven by iron-dependent lipid peroxidation, is closely associated with disruptions in iron homeostasis, lipid metabolism, and amino acid metabolism. This unique iron-catalysed death process plays a crucial role in both tumor initiation and malignant progression by disturbing cellular redox imbalance. The cystine/glutamate antiporter SLC7A11 (also known as xCT) has been identified as a central regulator of ferroptosis susceptibility. The tumor suppressor p53 and its associated microRNAs modulate ferroptotic responses through regulation of SLC7A11 expression, forming a critical axis in oncogenic transformation and metastasis. However, the precise role of SLC7A11 in CRC-particularly its context-dependent dual functions as both a tumor promoter and a therapeutic vulnerability-remains a critical unanswered question. This review aims to systematically summarize current advances in understanding the multiple roles of SLC7A11 in CRC-related ferroptosis pathways and to evaluate emerging therapeutic strategies targeting this axis. Importantly, we also underscore the existing knowledge gaps and outline future research directions essential for leveraging this unique molecular pathway to improve patient outcomes.