Overexpression of COUP‑TFII suppresses proliferation and metastasis of human gastric cancer cells

Abstract

The abnormal expression of the chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII) is associated with numerous forms of cancer, including gastric, prostate, colon and lung cancer. However, previous studies investigating the association between COUP-TFII expression and the occurrence, recurrence, invasion and metastasis of gastric cancer are limited in number. In the present study, it was revealed that the expression of COUP-TFII is significantly reduced in gastric carcinoma tissues compared with normal gastric mucosa cells (GES-1). In addition, the expression of COUP-TFII was also reduced in gastric cancer cell lines compared with GES-1 cells. Furthermore, it was revealed that ectopic expression of COUP-TFII was able to suppress the proliferation, migration and invasion of gastric cells, as well as inhibit hepatic metastasis, in vivo. In addition, it was demonstrated that COUP-TFII knockdown was able to promote the proliferation, migration and invasion of GES-1 cells in vitro. Furthermore, database analysis suggested that COUP-TFII expression in patients with gastric cancer is correlated with clinical stage classification and increased expression levels of COUP-TFII improved overall survival rates in patients with gastric cancer. The results of the present study suggest that COUP-TFII functions as a significant regulatory suppressor of gastric cancer growth and metastasis, and suggests that COUP-TFII may serve as a novel diagnostic and prognostic biomarker for gastric cancer metastasis.

COUP-TFII in Health and Disease

“…The ability to direct angiogenesis is paralleled by its role in mesenchymal cell differentiation and point to a role of the NR in regulating the cells micro-environment with evident implications for several pathologies [45,54,74,95,117,128,132,146]. Indeed, the NR expression (or the absence thereof) is associated with the unfavorable progression of malignancies in several organs [157,163,165,167,173,181]; besides, COUP-TFII is linked to pathologies considered cancer risk factors, such as diabetes or cirrhosis [54,64].…”

“…In line with this finding, COUP-TFII is more expressed in normal gastric mucosa cells (GES-1) compared with gastric cancer cells and gastric carcinoma tissues. Moreover, GES-1 cells with COUP-TFII knocked down have increased proliferation and invasiveness while COUP-TFII overexpression in xenograft tumor models reduces the tumor burden [165]. Finally, confronting the pathological data from 80 gastric cancer patients obtained from the Oncomine database, Ding et al demonstrated that high expression of COUP-TFII correlates with increased survival [165], in stark contrast with the results of Feng et al [166].…”

“…Onco-suppressor (?) [164,165] ↓proliferation ↓migration ↓invasiveness ↓cell growth ↓metastasis ↑survival rate Oncogene (?) [166] negative prognostic role Prostate cancer Oncogene [167][168][169][170][171][172] ↑tumor cell growth ↑proliferation ↑metastatic potential ↑invasion…”

“…Moreover, GES-1 cells with COUP-TFII knocked down have increased proliferation and invasiveness while COUP-TFII overexpression in xenograft tumor models reduces the tumor burden [165]. Finally, confronting the pathological data from 80 gastric cancer patients obtained from the Oncomine database, Ding et al demonstrated that high expression of COUP-TFII correlates with increased survival [165], in stark contrast with the results of Feng et al [166]. It is conceivable that this discrepancy arises from the use of different databases, the use of different selection criteria of the study population and the probe tested.…”

Recent progress on the role and molecular mechanism of chicken ovalbumin upstream promoter-transcription factor II in cancer

“…Ding et al 48 showed that COUP-TFII expression was reduced in gastric carcinoma tissues and gastric carcinoma cell lines compared with normal gastric mucosa tissues and normal gastric mucosa cells (GES-1), respectively. They also demonstrated that overexpressing COUP-TFII inhibited the proliferation, migration, and invasion of gastric cancer cells in vitro and inhibited the growth and hepatic metastasis of gastric cancer in vivo; however, they did not provide the underlying mechanisms for these activities of COUP-TFII in gastric cancer.…”