Role of triosephosphate isomerase and downstream functional genes on gastric cancer

Abstract

Triosephosphate isomerase (TPI) is highly expressed in many types of human tumors and is involved in migration and invasion of cancer cells. However, TPI clinicopathological significance and malignant function in gastric cancer (GC) have not been well defined. The present study aimed to examine TPI expression in GC tissue and its biological functions. Furthermore, we investigated its downstream genes by gene chip technology. Our results showed that TPI expression was higher in gastric cancer tissues than adjacent tissues, although no statistical differences were found between TPI expression and clinicopathological factors. TPI overexpression in human gastric carcinoma cell line BGC-823 enhanced cell proliferation, invasion and migration, but did not change cell cycle distribution, while TPI knockdown suppressed proliferation, invasion and migration, induced apoptosis and increased G2/M arrest of human gastric carcinoma cell line MGC-803. Since the cell division cycle associated 5 (CDCA5) was identified as the one with the most decreased expression after TPI knockdown, we investigated its role in MGC-803 cells. The results showed that CDCA5 knockdown also inhibited proliferation, migration, induced apoptosis and increased G2/M arrest similarly to TPI knockdown. CDCA5 overexpression promoted MGC-803 cell proliferation, clone formation and migration abilities. These results indicated that TPI expression level might affect GC cell behavior, suggesting that both TPI and CDCA5 might be considered as potential tumor markers related with GC development and might be potential new targets in GC treatment.

Therapeutic Targeting of Cancer Metabolism with Triosephosphate Isomerase

“…However, in recent years, the molecular mechanisms of the relationship between TPI and cancer progression have been started to be investigated. The results of the studies provide strong evidence that TPI enzyme may be involved in tumor progression, drug resistance, invasion and metastasis …”

“…TPI (EC 5.3.1.1.) is a key glycolytic enzyme that encoded by TPI gene located in 12p13 and main function of this enzyme is to catalyze the interconversion of dihydroxyacetone phosphate (DHAP) and glyceraldehyde‐3‐phosphate (G3P) during glycolysis and gluconeogenesis . Therefore, it has an essential role in the carbohydrate metabolism and energy production in all living cells.…”

“…In one of the recent studies, TPI has been defined as a potential tumor marker in gastric cancer . Chen et al .…”

“…In one of the recent studies, TPI has been defined as a potential tumor marker in gastric cancer . Chen et al . showed the overexpression of TPI in gastric cancer tissues and the upregulation of TPI on mRNA levels in gastric cancer cell lines.…”

“…The results showed that patients with higher TPI expression levels have shorter survival when compared to patients with lower TPI expression. According to these results, it is suggested that TPI level may effect on cancer cells behavior in gastric cancer, and may be considered a potential tumor marker and a new target in gastric cancer treatment . In order to elucidate the mechanism of the effect of TPI on gastric cancer, Ouyang et al .…”