GW112, A Novel Antiapoptotic Protein That Promotes Tumor Growth

Abstract

GW112 is a novel gene that has little homology to other known genes. It is overexpressed in a number of human tumor types, especially in those of the digestive system. We show here that GW112 is associated with GRIM-19, a protein known to be involved in regulating cellular apoptosis. Functionally, GW112 could significantly attenuate the ability of GRIM19 to mediate retinoic acid-IFN-␤-mediated cellular apoptosis and apoptosis-related gene expression. In addition, GW112 demonstrated strong antiapoptotic effects in tumor cells treated with other stress exposures such as hydrogen peroxide. Finally, forced overexpression of GW112 in murine prostate tumor cells led to more rapid tumor formation in a syngeneic host. Taken together, our data suggest that GW112 is an important regulator of cell death that plays important roles in tumor cell survival and tumor growth.

Serum olfactomedin 4 (GW112, hGC‐1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients

“…It has been reported that olfactomedin 4 interacts with GRIM-19 to attenuate retinoic acid and interferon beta-mediated cellular apoptosis and transient expression of olfactomedin 4 promotes tumor growth in C57/BL/6 mice. 9 Therefore, overexpression of olfactomedin 4 may contribute to carcinogenesis by resistance to apoptosis at least in early stage GC. In contrast, in CRC, it has been reported that olfactomedin 4 down-regulation is found in late stage cases, and in patients with shorter survival.…”

“…8 Although OLFM4 is predominantly expressed in bone marrow, small intestine, colon and prostate, 8 the levels of expression are much lower in normal tissues than in GC tissues. 5 Enhanced olfactomedin 4 expression has been reported in GC by Northern blot analysis 9 and by immunostaining. 10 Because olfactomedin 4 is a secreted N-linked glycoprotein, olfactomedin 4 may serve as a specific serum biomarker for GC; however, the concentration of olfactomedin 4 in serum has not been investigated.…”

Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer

“…We show that APin protein (APIN), taxol resistance-associated gene 3 (TRAG3), cytochrome P450, family 2, subfamily W, polypeptide 1 (CYP2W1), melanoma inhibitory activity (MIA), matrix metalloproteinase-10 (MMP-10), dickkopf homolog 4 (DKK4), GW112, regenerating islet-derived family, member 4 (REGIV), and HORMA domain-containing 1 (HORMAD1) were much more highly expressed in GC than in normal tissues. Among these genes, overexpression of REGIV and GW112 in GC has been reported (Oue et al, , 2005Zhang et al, 2004). Immunohistochemical analysis of MIA, MMP-10, and DKK4 in 151 GC samples revealed that MIA and MMP-10 are frequently overexpressed in GC.…”

Olfactomedin III expression contributes to anoikis-resistance in clonal variants of a human lung squamous carcinoma cell line

“…For example, OLFM4 was found to interact with and inhibit the apoptosis promoting factor GRIM-19 [41]. Alternatively, secreted OLFM3 may interact with cell surface receptors or secreted proteins to prevent anoikis signalling.…”