Stem cell marker olfactomedin 4: critical appraisal of its characteristics and role in tumorigenesis.

Olfactomedin 4 (OLFM4), a member of the olfactomedin domain-containing proteins, is a glycoprotein with molecular weight of approximately 64 kDa. The protein is a "robust marker" of Lgr5+ stem cells and has been localised to mitochondria, nuclei and cell membranes. The bulk of OLFM4 exists in a polymeric form which is held together by disulfide bonds and carbohydrate interactions. Earlier studies revealed that the protein binds to lectins and cadherins, and facilitates cell-cell adhesion. Recent data demonstrated that the protein possesses several hallmarks of carcinogenesis. OLFM4 has also been purported to be an inducible resistance factor to apoptotic stimuli such as radiation and anticancer drugs. Here, we review its synonyms and classification, gene structure, protein structure, intracellular and tissue distribution, adhesive and antiapoptotic; mitotic; migratory and cell cycle regulatory characteristics. We also critically evaluate recent advances in understanding of the transcriptional regulation of OLFM4 and its upstream signalling pathways with special emphasis on carcinogenesis and outline future perspectives in the field.