The SSEA-4 (Stage-Specific Embryonic Antigen-4) is a significant glycolipid antigen belonging to the Globo series glycosphingolipids (such as Gb5 and SSEA-3). Its structural characteristic is Neu5Gcα2-3Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-Cer. It is highly expressed during early embryonic development (e.g., in morula and blastocyst stages) and in pluripotent stem cells (such as human embryonic stem cells, hESCs, and induced pluripotent stem cells, iPSCs), making it a widely used surface marker for pluripotency. Additionally, SSEA-4 is aberrantly expressed in various cancers (e.g., breast cancer, lung cancer, gliomas) and is associated with tumor progression, metastasis, and immune evasion, potentially through the regulation of cell adhesion or signaling pathways (e.g., EGFR/ERK). Notably, since humans lack the enzyme to synthesize its sialic acid component (Neu5Gc), SSEA-4 expression may rely on exogenous uptake or non-canonical biosynthetic pathways. This unique feature also presents a potential therapeutic target for cancer treatment.
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