KRCC1: A potential therapeutic target in ovarian cancer
| العنوان: | KRCC1: A potential therapeutic target in ovarian cancer |
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| المؤلفون: | Yue Wang, Udayan Bhattacharya, Soumyajit Banerjee Mustafi, Fiifi Neizer-Ashun, Shailendra Kumar Dhar Dwivedi, Da Yang, Priyabrata Mukherjee, Xunhao Xiong, Cristina Ivan, Khader Shameer, Geeta Rao, Jonathan D. Wren, Chao Xu, Resham Bhattacharya, Anindya Dey, Joel T. Dudley |
| المصدر: | FASEB J |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Transcription, Genetic, DNA damage, Histone Deacetylase 2, Histone Deacetylase 1, Biochemistry, Article, Histones, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Cell Line, Tumor, Genetics, medicine, Humans, Gene silencing, Phosphorylation, Molecular Biology, Ovarian Neoplasms, biology, Intracellular Signaling Peptides and Proteins, medicine.disease, HDAC1, Neoplasm Proteins, 030104 developmental biology, Histone, Apoptosis, Acetylation, biology.protein, Cancer research, Female, Ovarian cancer, 030217 neurology & neurosurgery, DNA Damage, Biotechnology |
| الوصف: | Using a systems biology approach to prioritize potential points of intervention in ovarian cancer, we identified the lysine rich coiled-coil 1 (KRCC1), as a potential target. High-grade serous ovarian cancer patient tumors and cells express significantly higher levels of KRCC1 which correlates with poor overall survival and chemoresistance. We demonstrate that KRCC1 is predominantly present in the chromatin-bound nuclear fraction, interacts with HDAC1, HDAC2, and with the serine-threonine phosphatase PP1CC. Silencing KRCC1 inhibits cellular plasticity, invasive properties, and potentiates apoptosis resulting in reduced tumor growth. These phenotypes are associated with increased acetylation of histones and with increased phosphorylation of H2AX and CHK1, suggesting the modulation of transcription and DNA damage that may be mediated by the action of HDAC and PP1CC, respectively. Hence, we address an urgent need to develop new targets in cancer. |
| تدمد: | 1530-6860 0892-6638 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a783ede2e6a05572cd8123253d6c1d77Test https://doi.org/10.1096/fj.201902259rTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a783ede2e6a05572cd8123253d6c1d77 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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