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

Abstract

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.

Targeting Olfactomedin-like 3 Inhibits Tumor Growth by Impairing Angiogenesis and Pericyte Coverage

“…Olfml3 belongs to a family of olfactomedin domain-containing proteins with distinct roles in embryonic patterning, cell-cycle regulation, tumorigenesis, and ability to modulate critical signaling circuits such as Notch or Wnt pathways (21,22). Xenopus ONT1 serves as a scaffold protein that recruits the BMP1/Tolloid proteases to their substrate chordin, a BMP antagonist (19).…”

Detection and Clinical Significance of Circulating Tumor Cells in Colorectal Cancer—20 Years of Progress

“…We have tested the differential expression of several stem cell markers such as LGR5, olfactomedin 4 (OLFM4), achaetescute complex homolog 2 (ASCL2) and B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) (49,50) between CRC patients' tumor tissue and their matched normal mucosa. OLFM4 and LGR5 were overexpressed ≥2-fold in 18/22 (82%), ASCL2 in 13/22 (59%) and BMI-1 in 9/22 (41%) tumors (Figure 2).…”

“…OLFM4 and LGR5 were overexpressed ≥2-fold in 18/22 (82%), ASCL2 in 13/22 (59%) and BMI-1 in 9/22 (41%) tumors (Figure 2). OLFM4 has previously been identified as a good marker of intestinal stem cells and is involved in regulation of cell adhesion and organization of the cytoskeleton (50,51).…”

Plasma olfactomedin 4 level in peripheral blood and its association with clinical features of breast cancer

“…The encoded protein product, OLFM4, is a member of the olfactomedin-domain family with intracellular localization mostly in the mitochondria. OLFM4 is characterized by a coiled-coil domain at the N-terminus and a conserved olfactomedin domain of ~250 amino acids at the C-terminus (1). OLFM4 commonly exists in gastrointestinal epithelial cells, prostate and bone marrow (2,3), where it participates in cellular processes, including proliferation, apoptosis, metabolism and differentiation (4).…”

“…Furthermore, it was thought that the OLFM4 expression level has no significant association with common clinical variables (9,10). However, a limited number of studies have reported OLFM4 gene expression in breast cancer patients, and the expression levels of this gene in the peripheral blood of tumor patients remain to be documented (1,10,11,17). To assess the association of OLFM4 gene expression with the development and progression of breast cancer, breast cancer tissue and peripheral blood specimens were selected from patients of different histological grades, and these specimens were used to detect OLFM4 expression in the present study.…”