title: Targeted knockdown of polo-like kinase 1 alters metabolic regulation in melanoma.
abstract: A limited number of studies have indicated an association of the mitotic kinase polo-like kinase 1 (PLK1) and cellular metabolism. Here, employing an inducible RNA interference approach in A375 melanoma cells coupled with a PCR array and multiple validation approaches, we demonstrated that PLK1 alters a number of genes associated with cellular metabolism. PLK1 knockdown resulted in a significant downregulation of IDH1, PDP2 and PCK1 and upregulation of FBP1. Ingenuity Pathway Analysis (IPA) identified that 1) glycolysis and the pentose phosphate pathway are major canonical pathways associated with PLK1, and 2) PLK1 inhibition-modulated genes were largely associated with cellular proliferation, with FBP1 being the key modulator. Further, BI 6727-mediated inhibition of PLK1 caused a decrease in PCK1 and increase in FBP1 in A375 melanoma cell implanted xenografts in vivo. Furthermore, an inverse correlation between PLK1 and FBP1 was found in melanoma cells, with FBP1 expression significantly downregulated in a panel of melanoma cells. In addition, BI 6727 treatment resulted in an upregulation in FBP1 in A375, Hs294T and G361 melanoma cells. Overall, our study suggests that PLK1 may be an important regulator of metabolism maintenance in melanoma cells.
authors.affiliation: Department of Dermatology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Rosie Elizabeth Ann
authors.initials: RE
authors.lastname: Gutteridge
authors.affiliation: Department of Dermatology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Chandra K
authors.initials: CK
authors.lastname: Singh
authors.affiliation: Department of Dermatology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Ndiaye
authors.affiliation: Department of Dermatology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA; William S. Middleton VA Medical Center, 2500 Overlook Terrace, Madison, WI 53705, USA. Electronic address: nahmad@wisc.edu.
authors.forename: Nihal
authors.initials: N
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D004734:Energy Metabolism; D006597:Fructose-Bisphosphatase / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014162:Transfection; D047368:Tumor Burden; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D006597:Fructose-Bisphosphatase; D047908:Intracellular Signaling Peptides and Proteins; D007521:Isocitrate Dehydrogenase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase; D000097869:Polo-Like Kinase 1; C543588:IDH1 protein, human; C521898:PCK1 protein, human
keywords: Melanoma; Metabolism; Polo like kinase