title: Polo-like kinase 1 (Plk1) is expressed by cutaneous T-cell lymphomas (CTCLs), and its downregulation promotes cell cycle arrest and apoptosis.
abstract: Polo-like kinases are serine/threonine kinases crucial for mitosis and DNA integrity. Plk1, the most well studied member of this family, is upregulated in several cancers, as well as in dividing cells with peak expression during G2/M phase. Recently, employing lesional skin from patients with cutaneous T-cell lymphoma (CTCL), we showed that Plk1 was increased mainly in advanced lesions. In this study, employing western blot and quantitative RT-PCR analyses, we demonstrated that Plk1 was overexpressed in multiple CTCL cell lines (HH, Hut78, MyLa, SeAx and SZ4). Further, a genetic knockdown (by short hairpin RNA) or enzyme activity inhibition (via a small molecule inhibitor, GW843682X) was found to result in a decrease in cell growth, viability and proliferation. Plk1 inhibition in CTCL cells also resulted in: (1) increased G(2)/M phase cell cycle arrest, (2) alteration in key mitotic proteins, (3) apoptosis and (4) multiple mitotic errors. Given our findings, clinical trials of Plk1 inhibitors in CTCL may be a promising area for further translational investigation. We speculate that overexpression of Plk1 may prove to be relevant to the progression and prognosis of CTCL through its direct impact on the regulation of tumor cell proliferation and indirect influence on the acquisition of somatic mutations by proliferating tumor cells.
authors: Department of Dermatology, University of Wisconsin School of Medicine and Public Health and Paul P. Carbone Comprehensive Cancer Center, Madison, WI, USA.
authors: Minakshi
authors: M
authors: Nihal
authors: Nathalie
authors: N
authors: Stutz
authors: Travis
authors: T
authors: Schmit
authors: Nihal
authors: N
authors: Ahmad
authors: Gary S
authors: GS
authors: Wood
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use; D000097869:Polo-Like Kinase 1
chemical_list: D001562:Benzimidazoles; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D013876:Thiophenes; D000097869:Polo-Like Kinase 1; C524135:5-(5,6-dimethoxy-1H-benzimidazol-1-yl)-3-((2-(trifluoromethyl)benzyl)oxy)thiophene-2-carboxamide