Gene

Cell biology

SOX2

Biology

Missense mutation

Somatic cell

Mutation

Cancer research

Genetics

Embryonic stem cell

Gastrulation

Endoderm

Transcription factor

Transactivation

Cell

Reprogramming

Wnt signaling pathway

Cellular differentiation

Seminars in Cancer Biology

SOX17 is a transcription factor directing the specification and development of the primitive endoderm, primitive germ cells, definitive endoderm and, subsequently, is involved in the cardiovascular system and several endoderm-derived organs. The analysis of cancer genome sequencing data classified SOX17 as mutated cancer driver gene in endometrial cancer. These studies identified hotspot missense mutations within its DNA binding and transactivation domains. In somatic cell reprogramming, structure-based protein re-engineering showed a single missense mutation in SOX17 can change the DNA dependent heterodimer formation with OCT4 and enables the replacement of SOX2 with SOX17 mutants to induce pluripotency. This reveals the profound impact of specific missense mutations on gene function and regulatory activity. Here, we review the roles of SOX17 in cancer and discuss its cross-talk with the WNT/β-catenin pathway, potentially reconciling its activity as re-engineered reprogramming factor and mutated cancer driver gene.

SOX17 in cellular reprogramming and cancer