title: 6-Phosphogluconate dehydrogenase regulates tumor cell migration in vitro by regulating receptor tyrosine kinase c-Met.
abstract: 6-Phosphogluconate dehydrogenase (6PGD) is the third enzyme in the oxidative pentose phosphate pathway (PPP). Recently, we reported that knockdown of 6PGD inhibited lung tumor growth in vitro and in a xenograft model in mice. In this study, we continued to examine the functional role of 6PGD in cancer. We show that 6PGD expression positively correlates with advancing stage of lung carcinoma. In search of functional signals related to 6PGD, we discovered that knockdown of 6PGD significantly inhibited phosphorylation of c-Met at tyrosine residues known to be critical for activity. This downregulation of c-Met phosphorylation correlated with inhibition of cell migration in vitro. Overexpression of a constitutively active c-Met specifically rescued the migration but not proliferation phenotype of 6PGD knockdown. Therefore, 6PGD appears to be required for efficient c-Met signaling and migration of tumor cells in vitro.
authors: Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States. Electronic address: cchan@bidmc.harvard.edu.
authors: Barden
authors: B
authors: Chan
authors: Paul A
authors: PA
authors: VanderLaan
authors: Vikas P
authors: VP
authors: Sukhatme
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009367:Neoplasm Staging; D010734:Phosphogluconate Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D010734:Phosphogluconate Dehydrogenase; D019859:Proto-Oncogene Proteins c-met
keywords: 6-Phosphogluconate dehydrogenase; 6-phosphogluconate; 6PGD; FBS; Glucose metabolism; Glycolytic tumors; HGF; LDHA; Migration; PKM2; PPP; TPR-cMet; c-Met; fetal bovine serum; human hepatocyte growth factor; lactate dehydrogenase A; pentose phosphate pathway; pyruvate kinase M2