Phosphorylation of TCTP as a Marker for Polo-like Kinase-1 Activity In Vivo

Polo-like kinase 1 (PLK1) is the master regulator of mitosis and a target for anticancer therapy. To develop a marker of PLK1 activity in cells and tumour tissues, this study focused on translational controlled tumour protein (TCTP) and identified serine 46 as a site phosphorylated by PLK1 in vitro....

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Bibliographic Details
Published in:Anticancer research 2010-12, Vol.30 (12), p.4973-4985
Main Authors: CUCCHI, Ulisse, GIANELLINI, Laura M, GIORGINI, Maria L, CAPPELLA, Paolo, BERIA, Italo, VALSASINA, Barbara, DE PONTI, Anna, SOLA, Francesco, ALZANI, Rachele, PATTON, Veronica, PEZZONI, Alice, TROIANI, Sonia, SACCARDO, Maria B, RIZZI, Simona
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biomarkers, Tumor - metabolism
Bone Neoplasms - enzymology
Bone Neoplasms - metabolism
Cell Cycle - physiology
Cell Cycle Proteins - antagonists & inhibitors
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell Line, Tumor
Cell Nucleus - metabolism
Female
HCT116 Cells
Humans
Medical sciences
Mice
Mice, Nude
Osteosarcoma - enzymology
Osteosarcoma - metabolism
Ovarian Neoplasms - enzymology
Ovarian Neoplasms - metabolism
Phosphorylation
Polo-Like Kinase 1
Protein Serine-Threonine Kinases - antagonists & inhibitors
Protein Serine-Threonine Kinases - deficiency
Protein Serine-Threonine Kinases - genetics
Protein Serine-Threonine Kinases - metabolism
Proto-Oncogene Proteins - antagonists & inhibitors
Proto-Oncogene Proteins - deficiency
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - genetics
Tumor Protein, Translationally-Controlled 1
Tumors
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Summary:Polo-like kinase 1 (PLK1) is the master regulator of mitosis and a target for anticancer therapy. To develop a marker of PLK1 activity in cells and tumour tissues, this study focused on translational controlled tumour protein (TCTP) and identified serine 46 as a site phosphorylated by PLK1 in vitro. Using an antibody raised against phospho-TCTP-Ser46, it was demonstrated that phosphorylation at this site correlates with PLK1 level and kinase activity in cells. Moreover, PLK1 depletion by siRNA or inactivation by specific inhibitors caused a correspondent decrease in phospho-TCTP-Ser46 signal validating this site as a direct marker of PLK1. Using this marker, the study characterized PLK1 inhibitors in cells by setting up a high-content assay and finally immunohistochemical assay suitable for following inhibitor activity in preclinical tumour models and possibly in clinical studies was developed.
ISSN:0250-7005
1791-7530