Overexpression of autocrine motility factor in metastatic tumor cells: possible association with augmented expression of KIF3A and GDI-β

Abstract

Autocrine motility factor (AMF), which is identical to phosphohexose isomerase (PHI)/glucose-6-phosphate isomerase (GPI) , a ubiquitous enzyme essential for glycolysis, neuroleukin (NLK), a neurotrophic growth factor, and maturation factor (MF) mediating the differentiation of human myeloid cells, enhances the motility and metastatic ability of tumor cells. AMF/PHI activity is elevated in the serum or urine in patients with malignant tumors. Here, we constructed an amf/phi/nlk/mf gene using adenovirus vector and transfected into two tumor cell lines. Overexpression of AMF/PHI/NLK/MF enhanced AMF secretion into the culture media in both tumor cell lines. However, upregulation of motility and metastatic ability was found only in metastatic fibrosarcoma cells expressing an AMF receptor, gp78, and was not found in gp78-undetectable osteosarcoma cells. Thus, not only serum AMF activity but also gp78-expression in tumor cells may be required for metastasis-related motility induction. With the use of microarray analyses, we detected two augmented genes, rho GDP dissociation inhibitor beta and kinesin motor 3A, as well as AMF itself. The RNA message and protein expression of these two molecules was confirmed to be upregulated, suggesting a possible association with AMF-induced signaling for cell motility and metastasis.

Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling

“…A larger number of genes thought to be associated with tumorigenesis have been shown to be overexpressed in TOVs in our microarray analysis. These include GPI whose expression correlates with increased motility and metastatic activity of tumor cells (Yanagawa et al, 2004) and whose overexpression in ovarian tumors has previously been reported (Lee et al, 2004).…”

Differential Responses of Myogenic C2C12 Cells to Hypoxia between Growth and Muscle-Induction Phases: Growth, Differentiation and Motility

“…After 24 hours, the phagokinetic tracks were visualized using dark-field illumination under a Nikon inverted microscope. The area cleared of gold particles by at least 50 cells was measured using NIH image 1.62, and the standard error reflecting the 95% confidence level was calculated 39) .…”

Regulation of Phosphoglucose Isomerase/Autocrine Motility Factor Activities by the Poly(ADP-Ribose) Polymerase Family-14

“…To find the proteins interacting with PGI/AMF, cDNA library screening was done using the CytoTrap two-hybrid system (Stratagene) according to the instruction manual. Briefly, mouse pgi/amf gene that had been generated as previously reported (18) was inserted into pSos vector to produce human son of sevenless (hSos) protein fused with mouse PGI/AMF, which was used as a bait protein. cDNA library originated from mouse smooth muscle and inserted into pMyr vector that contains DNA encoding the myristylation membrane localization signal (Myr) was also purchased from Stratagene.…”

“…The signaling pathways downstream of AMFR include protein kinase CK2 (17), Rho family regulators, the rho GDP dissociation inhibitor h, and kinesin motor 3A, and is implicated in epithelial-mesenchymal transition by down-regulation of Ecadherin expression through the up-regulation of its transcription suppressor (e.g., Snail; refs. 18,19). We cloned the human and the mouse gp78/AMFR genes that were found to encode a novel conserved seven-transmembrane protein harboring a RING-H2 motif and a leucine zipper motif (20).…”