Cancers, Vol. 11, Pages 1025: Palbociclib Promotes Dephosphorylation of NPM/B23 at Threonine 199 and Inhibits Endometrial Cancer Cell Growth

Cancers, Vol. 11, Pages 1025: Palbociclib Promotes Dephosphorylation of NPM/B23 at Threonine 199 and Inhibits Endometrial Cancer Cell Growth Cancers doi: 10.3390/cancers11071025 Authors: Chiao-Yun Lin Li-Yu Lee Tzu-Hao Wang Cheng-Lung Hsu Chia-Lung Tsai Angel Chao Chyong-Huey Lai Endometrial cancer incidence rates are growing, especially in countries with rapid socioeconomic transitions. Despite recent advances in chemotherapy, hormone therapy, and targeted therapy, advanced/recurrent disease remains a clinical challenge. Palbociclib—a selective inhibitor of cyclin-dependent kinases (CDK) 4/6—has therapeutic potential against estrogen receptor (ER)-positive and HER2-negative breast cancer. However, the question as to whether it can be clinically useful in endometrial cancer remains open. Here, we show that combined treatment with palbociclib and megesterol acetate exerts synergistic antiproliferative effects against endometrial cancer cells. Treatment of cancer cells with palbociclib suppressed NPM/B23 phosphorylation at threonine 199 (Thr199). We further demonstrated that CDK6 acts as a NPM/B23 kinase. Palbociclib-induced NPM/B23 dephosphorylation sensitized endometrial cancer cells to megesterol acetate through the upregulation of ERα expression. Immunohistochemistry revealed an overexpression of phospho-NPM/B23 (Thr199) in human endometrial cancer, and phospho-NPM/B23 (Thr199) expression levels were inversely associated wit...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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This study is an important step forward in highlighting C1q as a new prognostic candidate biomarker for a range of carcinomas. Methods Oncomine Database Analysis The expression levels of C1QA, C1QB, and C1QC genes in various carcinomas were analyzed using Oncomine (www.oncomine.org), a cancer microarray database and web-based data mining platform from genome-wide expression analyses (22, 23). We compared the differences in mRNA level between normal tissue and carcinoma. The mRNA expression levels in neoplastic tissues compared to the healthy tissues were obtained as the parameters of p-value 2, and gene ranking in the t...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Li Liu, Jiajing Lin and Hongying He* Department of Obstetrics and Gynecology, Liuzhou Worker’s Hospital, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China Background and Objective: Endometrial cancer (EC) is a common gynecological malignancy worldwide. Despite advances in the development of strategies for treating EC, prognosis of the disease remains unsatisfactory, especially for advanced EC. The aim of this study was to identify novel genes that can be used as potential biomarkers for identifying the prognosis of EC and to construct a novel risk stratification using these genes. Me...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionsThe introduction of HER2-directed therapies has dramatically influenced the outcome of patients with HER2 positive breast and gastric/gastroesophageal cancers. The present study findings provided that HER-2/neu expression in patients with OC has an adverse impact on the PFS. Therefore, our results show that the decision algorithm usually used in breast cancer by HER2 may be appropriate in ovarian cancer.
Source: The Journal of Obstetrics and Gynecology of India - Category: OBGYN Source Type: research
Conclusions: Our study suggests 125I-Herceptin can be used as an effective SPECT probe for the non-invasive detection of colon cancer expressing HER2. Research Support: This work is supported by the National Natural Science Foundation of China (Grant No. 81471714) and the Staring Foundation for Young Researcher of Changhai Hospital (Grant No. CH201714).
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Science Posters (Oncology) Source Type: research
(Queen Mary University of London) Researchers at Queen Mary University of London have discovered that the loss of a single protein- PHLDA1- is sufficient for the development of drug resistance to a type of targeted therapy in endometrial and HER2-positive breast cancer cells.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Publication date: 27 February 2018 Source:Cell Reports, Volume 22, Issue 9 Author(s): Abbie E. Fearon, Edward P. Carter, Natasha S. Clayton, Edmund H. Wilkes, Ann-Marie Baker, Ekaterina Kapitonova, Bakhouche A. Bakhouche, Yasmine Tanner, Jun Wang, Emanuela Gadaleta, Claude Chelala, Kate M. Moore, John F. Marshall, Juliette Chupin, Peter Schmid, J. Louise Jones, Michelle Lockley, Pedro R. Cutillas, Richard P. Grose Development of resistance causes failure of drugs targeting receptor tyrosine kinase (RTK) networks and represents a critical challenge for precision medicine. Here, we show that PHLDA1 downregulation is critica...
Source: Cell Reports - Category: Cytology Source Type: research
Conditions:   Triple Negative Breast Cancer;   Endometrial Cancer;   Hormone Receptor Positive, HER2 Negative Breast Cancer Intervention:   Drug: ONC201 Sponsor:   National Cancer Institute (NCI) Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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