Human-specific elimination of epithelial Siglec-XII suppresses the risk of inflammation-driven colorectal cancers.

ABSTRACT: Carcinomas are common in humans but rare among closely related "great apes." Plausible explanations, including human-specific genomic alterations affecting the biology of sialic acids, are proposed, but causality remains unproven. Here, an integrated evolutionary genetics-phenome-transcriptome approach studied the role of SIGLEC12 gene (encoding Siglec-XII) in epithelial transformation and cancer. Exogenous expression of the protein in cell lines and genetically engineered mice recapitulated approximately 30% of the human population in whom the protein is expressed in a form that cannot bind ligand because of a fixed, homozygous, human-universal missense mutation. Siglec-XII-null cells/mice recapitulated the remaining approximately 70% of the human population in whom an additional polymorp

SUBMITTER: Cuello HA 

PROVIDER: S-EPMC11343606 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature