The TIGD5 gene located in 8q24 and frequently amplified in ovarian cancers is a tumor suppressor

Abstract

Ovarian cancer (OC) is the fifth most common cancer of female cancer death and leading cause of lethal gynecological cancers. High‐grade serous ovarian carcinoma (HGSOC) is an aggressive malignancy that is rapidly fatal. Many cases of OC show amplification of the 8q24 chromosomal region, which contains the well‐known oncogene MYC. Although MYC amplification is more frequently observed in OCs than in other tumor types, due to the large size of the 8q24 amplicon, the functions of the vast majority of the genes it contains are still unknown. The TIGD5 gene is located at 8q24.3 and encodes a nuclear protein with a DNA‐binding motif, but its precise role is obscure. We show here that TIGD5 often co‐amplifies with MYC in OCs, and that OC patients with high TIGD5 mRNA expression have a poor prognosis. However, we also found that TIGD5 overexpression in ovarian cancer cell lines unexpectedly suppressed their growth, adhesion, and invasion in vitro, and also reduced tumor growth in xenografted nude mice in vivo. Thus, our work suggests that TIGD5 may in fact operate as a tumor suppressor in OCs rather than as an oncogene.

ProteasomeID: quantitative mapping of proteasome interactomes and substrates forin vitroandin vivostudies

“…TIGD5 encodes protein with DNA-binding features. Though its exact function is not established, it has been suggested to operate as a tumor suppressor in ovarian cancer 44 . We then performed a cycloheximide chase experiment and could validate them as proteasome substrates (Figure 4g and S4j).…”