Lewis X (Le^x, CD15, SSEA-1) is a trisaccharide carbohydrate antigen with the structure Galβ(1-4)[Fucα(1-3)]GlcNAc, prominently expressed on glycoconjugates in neural stem cells, granulocytes, and various tumors. This glycan serves as a marker of undifferentiated cells and mediates key cellular processes through its fucosylated motif. Biosynthesis involves fucosyltransferase 9 (FUT9), which adds the fucose residue to N-glycans, as demonstrated in neural stem cell studies where FUT9 suppression depleted Le^x and impaired proliferation.

Functions in Stem Cell Maintenance

In mouse embryonic neural stem cells, Le^x on N-glycans activates the Notch signaling pathway, upregulating Musashi-1 to promote proliferation and maintain stemness without inducing apoptosis. Pax6 regulates FUT9 expression, linking Le^x to self-renewal and neurogenesis in the developing brain. Le^x also supports cellular aggregation and migration in neural stem cells, highlighting its role in early neural development.

Roles in Immunity and Inflammation

Le^x on polymorphonuclear granulocytes facilitates adhesion during immune responses, with expression on monocytes and activated lymphocytes aiding extravasation. Unlike its sialylated counterpart (sialyl Le^x), Le^x acts as a marker rather than a primary selectin ligand in inflammation. High expression occurs in normal epithelia, underscoring its physiological prevalence beyond pathology.

Implications in Cancer and Metastasis

Aberrant Le^x expression appears on tumors like colon, breast carcinoma, and leukemia, where it contributes to glycoprotein modifications alongside sialyl Le^x on mucins such as MUC1. While sialyl Le^x drives metastasis via E-selectin binding, Le^x shows dual roles, with antibodies distinguishing it in tumor profiling. Studies position Le^x as a target for cancer immunotherapy, often alongside Le^y.