Phosphoglucose isomerase enhances colorectal cancer metastasis

Abstract

Abstract. Phosphoglucose isomerase (PGI) is a ubiquitous cytosolic enzyme that plays a key role in glycolysis. PGI is also a multifunctional protein that acts in the extracellular milieu as a potent mitogen/cytokine. Increased expression of PGI and its receptor has been found in a wide spectrum of malignancies and is associated with cancer progression and metastasis. In this study, the role of PGI in the growth and metastasis of colon cancer cells was determined. To elucidate the functional role of PGI in colorectal cancer, we stably transfected PGI cDNA into human colon cancer cells. We used an orthotopic mouse tumor model to assess whether overexpression of PGI enhances liver metastasis. Overexpression of PGI stimulated the in vitro invasion of DLD-1 cells. In vivo, after orthotopic implantation into the cecum of nude mice, parental and empty vector-transfected DLD-1 cells produced small tumors without liver metastasis, whereas PGI-overexpressing DLD-1 cells produced large tumors and liver metastases. In conclusion, overexpression of PGI significantly contributes to the aggressive phenotype of human colon cancer and, thus, may provide a novel therapeutic target.

Targeting the Metabolic Reprogramming That Controls Epithelial-to-Mesenchymal Transition in Aggressive Tumors

“…Furthermore, lonidamine that targets mitochondria-bound HK is now tested in phase II–III clinical trials (89). The HIF-1 dependent PGI/AMF (see above) acts as a pro-metastatic signaling molecule, due to its ability to promote tumor migration, invasion, and metastasis (90–92). Indeed, PGI/AMF overexpression leads to EMT achievement through NF-κB activation and increased expression of Snail1, ZEB1, and ZEB2 (Figure 2), downregulation of miR-200s with concomitant loss of E-cadherin (93).…”

Advances in glucose metabolism research in colorectal cancer

“…Tsutsumi et al (31) determined that overexpression of PGI significantly contributes to the aggressive phenotype of human colon cancer and, thus, may provide a novel therapeutic target.…”

Anticancer Agents That Counteract Tumor Glycolysis

“…The levels of GPI/AMF were found to be elevated in patients with a wide range of tumors and are strictly associated with cancer progression, angiogenesis, and metastasis. [118–122] It was also reported that the expression of GPI/AMF is up-regulated in some tumor cells by hypoxia and that hypoxia-induced GPI/AMF m RNA expression is controlled, at least in part, by HIF-1. [123] The stimulation of tumor cell motility is initiated by the binding of GPI/AMF to the AMF receptor (AMFR, gp78) on the cell surface, which is known to be a glycosylated seven transmembrane helix protein of 78 kDa with the C -terminal region expressed outside the cell.…”