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Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) is a multifunctional enzyme that functions in glucose metabolism as a glycolytic enzyme inside the cell, while acts as a cytokine outside the cell that exhibits motogenic, mitogenic, and differentiation activities. Up-regulation of PGI/AMF expression has been observed in many human malignant tumors, and thought to contribute to an increase of cell growth and a resistance to cellular stress. We report here that PGI/AMF is involved in cellular senescence as a tumor suppressive mechanism. The stably transfected with siRNA targeting PGI/AMF tumor cells, which exhibited a marked inhibited expression of endogenous PGI/AMF protein and completely decreased secreted PGI/AMF protein, significantly decreased cell growth and proliferation, and showed the inhibition of the G1 to S transition in the cell cycle. PGI/AMF knockdown cells resulted in a significant decrease in telomerase reverse transcriptase expression and increase in senescence-associated ß-galactosidase activity. Furthermore, we found that PGI/AMF negatively regulated the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1, key effectors of cellular senescence. PGI/AMF also decreased the transcription factor p53 expression. These results suggest that the expression of PGI/AMF is critically required to maintain proliferation and suppress senescence in tumor cells.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

American Association for Cancer Research
2007