FUCA1, encoding lysosomal α-L-fucosidase-1 enzyme, is a p53 target gene [1,3]. It plays a crucial role in fucosylation, a type of glycosylation modifying cellular biomolecules, which has a significant impact on cellular function and carcinogenesis [1]. Glycosylation is involved in multiple cancer-promoting mechanisms such as EGFR, PI3K/Akt, and p53-mediated pathways [1].

In clear cell renal cell carcinoma (ccRCC), FUCA1 expression is downregulated, predicting poor prognosis. Enhancing its expression reduces ccRCC cell invasion and migration, suggesting it acts as a tumor suppressor [2]. CTCF, an upstream transcription factor of FUCA1, can reverse the effects of its inactivation [2]. In addition, FUCA1 may regulate the autophagy process in ccRCC cells by influencing the fusion between autophagosomes and lysosomes [2].

In osteosarcoma, FUCA1 is significantly enriched in non-metastatic cases, with higher expression correlating with better patient survival rates, and is related to immune functions such as macrophage phagocytosis and antigen presentation [5].

In colorectal cancer, USP35 promotes cell proliferation and chemotherapeutic resistance by stabilizing FUCA1 [4].

In thyroid cancers, FUCA1 expression levels vary depending on p53 status, being lower in anaplastic thyroid cancer samples (where p53 is mostly mutated) and higher in papillary thyroid cancer samples (where p53 is mostly wild-type) [3].

In summary, FUCA1 is essential in fucosylation and has a significant impact on cancer-related processes. Its downregulation in certain cancers like ccRCC and its relation to prognosis in multiple cancers suggest its potential as a biomarker and therapeutic target. Functional studies in cancer models have revealed its role in tumor suppression, autophagy regulation, and its connection to other molecules in the disease context [1,2,6-8].