keyword
MENU ▼
Read by QxMD icon Read
search

Plk1

keyword
https://www.readbyqxmd.com/read/27904765/volasertib-suppresses-the-growth-of-human-hepatocellular-carcinoma-in-vitro-and-in-vivo
#1
Di-Wei Zheng, You-Qiu Xue, Yong Li, Jin-Ming Di, Jian-Ge Qiu, Wen-Ji Zhang, Qi-Wei Jiang, Yang Yang, Yao Chen, Meng-Ning Wei, Jia-Rong Huang, Kun Wang, Xing Wei, Zhi Shi
Hepatocellular carcinoma (HCC) is the sixth most frequent malignant tumor with poor prognosis, and its clinical therapeutic outcome is poor. Volasertib, a potent small molecular inhibitor of polo-like kinase 1 (PLK1), is currently tested for treatment of multiple cancers in the clinical trials. However, the antitumor effect of volasertib on HCC is still unknown. In this study, our data show that volasertib is able to induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the spindle abnormalities in human HCC cells...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27902479/identification-of-a-novel-polo-like-kinase-1-inhibitor-that-specifically-blocks-the-functions-of-polo-box-domain
#2
Yunyu Chen, Jing Zhang, Dongsheng Li, Jiandong Jiang, Yanchang Wang, Shuyi Si
Polo-like kinase 1 (Plk1) is a promising target for cancer therapy due to its essential role in cell division. In addition to a highly conserved kinase domain, Plk1 also contains a Polo-Box domain (PBD), which is essential for Plk1's subcellular localization and mitotic functions. We adopted a fluorescence polarization assay and identified a new Plk1 PBD inhibitor T521 from a small-molecule compound library. T521 specifically inhibits the PBD of Plk1, but not those of Plk2-3. T521 exhibits covalent binding to some lysine residues of Plk1 PBD, which causes significant changes in the secondary structure of Plk1 PBD...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899378/cervical-cancer-growth-is-regulated-by-a-c-abl-plk1-signaling-axis
#3
Xu Yang, Gang Chen, Wei Li, Changmin Peng, Yue Zhu, Xiaoming Yang, Teng Li, Cheng Cao, Huadong Pei
The non-receptor tyrosine kinase c-ABL controls cell growth but its contributions in solid tumors are not fully understood. Here we report that the Polo-like kinase PLK1, an essential mitotic kinase regulator, is an important downstream effector of c-ABL in regulating the growth of cervical cancer. c-ABL interacted with and phosphorylated PLK1. Phosphorylation of PLK1 by c-ABL inhibited PLK1 ubiquitination and degradation and enhanced its activity, leading to cell cycle progression and tumor growth. Both c-ABL and PLK1 were overexpressed in cervical carcinoma...
November 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27888710/plk1-a-potential-target-for-cancer-therapy
#4
REVIEW
Zhixian Liu, Qingrong Sun, Xiaosheng Wang
Polo-like kinase 1 (PLK1) plays an important role in the initiation, maintenance, and completion of mitosis. Dysfunction of PLK1 may promote cancerous transformation and drive its progression. PLK1 overexpression has been found in a variety of human cancers and was associated with poor prognoses in cancers. Many studies have showed that inhibition of PLK1 could lead to death of cancer cells by interfering with multiple stages of mitosis. Thus, PLK1 is expected to be a potential target for cancer therapy. In this article, we examined PLK1's structural characteristics, its regulatory roles in cell mitosis, PLK1 expression, and its association with survival prognoses of cancer patients in a wide variety of cancer types, PLK1 interaction networks, and PLK1 inhibitors under investigation...
November 23, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27882722/designed-inhibitor-for-nuclear-localization-signal-of-polo-like-kinase-1-induces-mitotic-arrest
#5
Fangjin Chen, Xiaolong Zhuo, Tan Qin, Xiao Guo, Chuanmao Zhang, Luhua Lai
Polo-like kinase 1 (Plk1), a member of polo-like kinase family, regulates multiple essential steps of the cell cycle progression. Plk1 is overexpressed in multiple cancer cell lines and considered to be a prime anticancer target. Plk1 accumulates in the nucleus during S and G2 phases by its bipartite nuclear localization signal (NLS) sequence, which is crucial for Plk1 regulation during normal cell cycle progression. Here, through combined computational and experimental studies, we identified compound D110, which inhibits Plk1 kinase activity with an IC50 of 85 nm and blocks the nuclear localization of Plk1 during S and G2 phases...
November 24, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27878946/targeted-inhibition-of-polo-like-kinase-1-by-a-novel-small-molecule-inhibitor-induces-mitotic-catastrophe-and-apoptosis-in-human-bladder-cancer-cells
#6
Zhe Zhang, Guojun Zhang, Chuize Kong
Bladder cancer is a common cancer with particularly high recurrence after transurethral resection. Despite improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little. In this study, the anti-tumour activities of a novel Polo-like kinase 1 (PLK1) inhibitor (RO3280) was evaluated in vitro and in vivo in the bladder carcinoma cell lines 5637 and T24. MTT assays, colony-formation assays, flow cytometry, cell morphological analysis and trypan blue exclusion assays were used to examine the proliferation, cell cycle distribution and apoptosis of bladder carcinoma cells with or without RO3280 treatment...
November 23, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27874094/identification-of-polo-like-kinase-1-interaction-inhibitors-using-a-novel-cell-based-assay
#7
Karine Normandin, Jean-François Lavallée, Marie Futter, Alexandre Beautrait, Jean Duchaine, Sébastien Guiral, Anne Marinier, Vincent Archambault
Polo-like kinase 1 (Plk1) plays several roles in cell division and it is a recognized cancer drug target. Plk1 levels are elevated in cancer and several types of cancer cells are hypersensitive to Plk1 inhibition. Small molecule inhibitors of the kinase domain (KD) of Plk1 have been developed. Their selectivity is limited, which likely contributes to their toxicity. Polo-like kinases are characterized by a Polo-Box Domain (PBD), which mediates interactions with phosphorylation substrates or regulators. Inhibition of the PBD could allow better selectivity or result in different effects than inhibition of the KD...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871934/v-src-induced-nuclear-localization-of-yap-is-involved-in-multipolar-spindle-formation-in-tetraploid-cells
#8
Keiko Kakae, Masayoshi Ikeuchi, Takahisa Kuga, Youhei Saito, Naoto Yamaguchi, Yuji Nakayama
The protein-tyrosine kinase, c-Src, is involved in a variety of signaling events, including cell division. We have reported that v-Src, which is a mutant variant of the cellular proto-oncogene, c-Src, causes delocalization of Aurora B kinase, resulting in a furrow regression in cytokinesis and the generation of multinucleated cells. However, the effect of v-Src on mitotic spindle formation is unknown. Here we show that v-Src-expressing HCT116 and NIH3T3 cells undergo abnormal cell division, in which cells separate into more than two cells...
November 18, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27862999/assessment-of-bromodomain-target-engagement-by-a-series-of-bi2536-analogues-with-miniaturized-bet-bret
#9
Luke W Koblan, Dennis L Buckley, Christopher J Ott, Mark E Fitzgerald, Stuart W J Ember, Jin-Yi Zhu, Shuai Liu, Justin M Roberts, David Remillard, Sarah Vittori, Wei Zhang, Ernst Schonbrunn, James E Bradner
Evaluating the engagement of a small molecule ligand with a protein target in cells provides useful information for chemical probe optimization and pharmaceutical development. While several techniques exist that can be performed in a low-throughput manner, systematic evaluation of large compound libraries remains a challenge. In-cell engagement measurements are especially useful when evaluating compound classes suspected to target multiple cellular factors. In this study we used a bioluminescent resonant energy transfer assay to assess bromodomain engagement by a compound series containing bromodomain- and kinase-biasing polypharmacophores based on the known dual BRD4 bromodomain/PLK1 kinase inhibitor BI2536...
November 15, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27861885/sensitivity-of-tp53-mutated-cancer-cells-to-the-phytoestrogen-genistein-is-associated-with-direct-inhibition-of-plk1-activity
#10
Sol-Bi Shin, Sang-Uk Woo, Young Won Chin, Young-Joo Jang, Hyungshin Yim
Polo-like kinase 1 (Plk1), a conserved Ser/Thr mitotic kinase, has been identified as a promising target for anticancer drug development because its overexpression is correlated with malignancy. Here, we found that genistein, an isoflavone, inhibits Plk1 kinase activity directly. Previously the mitotic disturbance phenomenon induced by treatment with genistein was not fully explained by its inhibitory effect on EGFR. In kinase profiling assays, it showed selectivity relative to a panel of kinases, including EGFR...
November 9, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27857970/bora-dependent-plk1-regulation-a-new-weapon-for-cancer-therapy
#11
Luca Cirillo, Yann Thomas, Lionel Pintard, Monica Gotta
The mitotic kinase polo like kinase 1 (PLK1) is overexpressed in many cancers and its inhibition slows down proliferation and increases apoptosis in cancer cell lines. Understanding how PLK1 is activated is therefore crucial for the development of novel PLK1 inhibitors with anticancer properties. We recently identified a conserved regulatory loop leading to PLK1 activation that involves cyclin-dependent kinase 1 (CDK1).
2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27831827/mitotic-entry-the-interplay-between-cdk1-plk1-and-bora
#12
Alfonso Parrilla, Luca Cirillo, Yann Thomas, Monica Gotta, Lionel Pintard, Anna Santamaria
Polo-like kinase 1 (Plk1) is an important mitotic kinase that is crucial for entry into mitosis after recovery from DNA damage-induced cell cycle arrest. Plk1 activation is promoted by the conserved protein Bora (SPAT-1 in C. elegans), which stimulates the phosphorylation of a conserved residue in the activation loop by the Aurora A kinase. In a recent article published in Cell Reports, we show that the master mitotic kinase Cdk1 contributes to Plk1 activation through SPAT-1/Bora phosphorylation. We identified 3 conserved Sp/Tp residues that are located in the N-terminal, most conserved part, of SPAT-1/Bora...
November 10, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27830001/plk1-promotes-epithelial-mesenchymal-transition-and-metastasis-of-gastric-carcinoma-cells
#13
Xiao Peng Cai, Liang Dong Chen, Hai Bin Song, Chun Xiao Zhang, Ze Wei Yuan, Zhen Xian Xiang
Cancer cell epithelial-mesenchymal transition (EMT) is the crucial event for cancer progression and plays a vital role in the metastasis of cancer cells. Activation of Polo-like kinase 1 (PLK1) signaling has been implicated as the critical event in several tumor metastasis and EMT, however, whether PLK1 participates in gastric carcinoma metastasis and EMT still remains unclear. For this study, we elucidated the potential physiological function of PLK1 in the metastasis of gastric tumors, as well its distinct role in cells EMT and subsequently determined the mechanism involved in PLK1 regulated...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27826797/the-cohesion-stabilizer-sororin-favors-dna-repair-and-chromosome-segregation-during-mouse-oocyte-meiosis
#14
Chun-Jie Huang, Yi-Feng Yuan, Di Wu, Faheem Ahmed Khan, Xiao-Fei Jiao, Li-Jun Huo
Maintenance and timely termination of cohesion on chromosomes ensures accurate chromosome segregation to guard against aneuploidy in mammalian oocytes and subsequent chromosomally abnormal pregnancies. Sororin, a cohesion stabilizer whose relevance in antagonizing the anti-cohesive property of Wings-apart like protein (Wapl), has been characterized in mitosis; however, the role of Sororin remains unclear during mammalian oocyte meiosis. Here, we show that Sororin is required for DNA damage repair and cohesion maintenance on chromosomes, and consequently, for mouse oocyte meiotic program...
November 8, 2016: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27822032/co-delivery-of-doxorubicin-and-recombinant-plasmid-phsp70-plk1-shrna-by-bacterial-magnetosomes-for-osteosarcoma-therapy
#15
Li Cheng, Youqun Ke, Shuisheng Yu, Juehua Jing
To explore a novel combination of chemotherapy, gene therapy, and thermotherapy for osteosarcoma, a targeted heat-sensitive co-delivery system based on bacterial magnetosomes (BMs) was developed. The optimal culture conditions of magnetotactic bacteria (MTB) AMB-1 and characterization of BMs were achieved. A recombinant eukaryotic plasmid heat shock protein 70-polo-like kinase 1-short hairpin RNA (pHSP70-Plk1-shRNA) under transcriptional control of a thermosensitive promoter (human HSP70 promoter) was constructed for gene therapy...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27819275/the-pten-phosphatase-functions-cooperatively-with-the-fanconi-anemia-proteins-in-dna-crosslink-repair
#16
Elizabeth A Vuono, Ananda Mukherjee, David A Vierra, Morganne M Adroved, Charlotte Hodson, Andrew J Deans, Niall G Howlett
Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure and increased cancer risk. The FA proteins function primarily in DNA interstrand crosslink (ICL) repair. Here, we have examined the role of the PTEN phosphatase in this process. We have established that PTEN-deficient cells, like FA cells, exhibit increased cytotoxicity, chromosome structural aberrations, and error-prone mutagenic DNA repair following exposure to ICL-inducing agents. The increased ICL sensitivity of PTEN-deficient cells is caused, in part, by elevated PLK1 kinase-mediated phosphorylation of FANCM, constitutive FANCM polyubiquitination and degradation, and the consequent inefficient assembly of the FA core complex, FANCD2, and FANCI into DNA repair foci...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27802111/identification-of-differential-gene-expression-patterns-after-acute-exposure-to-high-and-low-doses-of-low-let-ionizing-radiation-in-a-reconstituted-human-skin-tissue
#17
Susan C Tilton, Lye Meng Markillie, Spencer Hays, Ronald C Taylor, David L Stenoien
In this study we utilized a systems biology approach to identify dose- (0.1, 2.0 and 10 Gy) and time- (3 and 8 h) dependent responses to acute ionizing radiation exposure in a complex tissue, reconstituted human skin. The low dose used here (0.1 Gy) falls within the range of certain medical diagnostic procedures. Of the two higher doses used, 2.0 Gy is typically administered for radiotherapy, while 10 Gy is lethal. Because exposure to any of these doses is possible after an intentional or accidental radiation events, biomarkers are needed to rapidly and accurately triage potentially exposed individuals...
November 2016: Radiation Research
https://www.readbyqxmd.com/read/27799364/five-factors-can-reconstitute-all-three-phases-of-microtubule-polymerization-dynamics
#18
Takashi Moriwaki, Gohta Goshima
Cytoplasmic microtubules (MTs) undergo growth, shrinkage, and pausing. However, how MT polymerization cycles are produced and spatiotemporally regulated at a molecular level is unclear, as the entire cycle has not been recapitulated in vitro with defined components. In this study, we reconstituted dynamic MT plus end behavior involving all three phases by mixing tubulin with five Drosophila melanogaster proteins (EB1, XMAP215(Msps), Sentin, kinesin-13(Klp10A), and CLASP(Mast/Orbit)). When singly mixed with tubulin, CLASP(Mast/Orbit) strongly inhibited MT catastrophe and reduced the growth rate...
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27793694/small-molecule-inhibition-of-polo-like-kinase-1-by-volasertib-bi-6727-causes-significant-melanoma-growth-delay-and-regression-in%C3%A2-vivo
#19
Brian D Cholewa, Mary A Ndiaye, Wei Huang, Xiaoqi Liu, Nihal Ahmad
The objective of this study was to determine the therapeutic potential of polo-like kinase 1 (Plk1) inhibition in melanoma, in vivo. Employing Vectra technology, we assessed the Plk1 expression profile in benign nevi, malignant (stages I-IV) and metastatic melanomas. We found a significant elevation of Plk1 immunostaining in melanoma tissues. Further, a second generation small molecule Plk1 inhibitor, BI 6727, resulted in reductions in growth, viability and clonogenic survival, as well as an increase in apoptosis of A375 and Hs 294T melanoma cells...
October 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27793187/a-combination-therapy-for-kras-mutant-lung-cancer-by-targeting-synthetic-lethal-partners-of-mutant-kras
#20
Xiufeng Pang, Mingyao Liu
The KRAS gene is frequently mutated in multiple cancer types, but it fell off the drug discovery radar for many years because of its inherent "undruggable" structure and undefined biological properties. As reported in the paper entitled "Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK" in Nature Communications, we performed a synthetic lethal screening with a combinatorial strategy on a panel of clinical drugs; we found that combined inhibition of polo-like kinase 1 and RhoA/Rho kinase markedly suppressed tumor growth in mice...
October 28, 2016: Chinese Journal of Cancer
keyword
keyword
85298
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"