التفاصيل البيبلوغرافية
| العنوان: |
An in vivo screen identifies PYGO2 as a driver for metastatic prostate cancer |
| المؤلفون: |
Chang-Jiun Wu, Yong Zang, Xiaolu Pan, Y. Alan Wang, Yanting Luo, Xin Lu, Shan Jiang, Eun-Jung Jin, Samirkumar B. Amin, Xiaoying Shang, Nora M. Navone, Xuemin Lu, William R. Morgenlander, Patricia Troncoso, Pingna Deng, Rumi Lee, Qing Chang, Ronald A. DePinho, Di Zhao, Jacqueline Weinrich, Sunada Khadka, Shan Feng |
| سنة النشر: |
2018 |
| مصطلحات موضوعية: |
0301 basic medicine, Male, Transcriptional Activation, Cancer Research, Carcinogenesis, Mice, Nude, Biology, medicine.disease_cause, Article, Metastasis, 03 medical and health sciences, Prostate cancer, Mice, Cell Line, Tumor, medicine, Biomarkers, Tumor, Animals, Humans, Wnt Signaling Pathway, Oncogene, Wnt signaling pathway, Intracellular Signaling Peptides and Proteins, Cancer, Prostatic Neoplasms, Oncogenes, medicine.disease, Primary tumor, Up-Regulation, Gene Expression Regulation, Neoplastic, 030104 developmental biology, HEK293 Cells, Oncology, Tumor progression, PC-3 Cells, Cancer research, Disease Progression, Lymph Nodes, Neoplasm Grading |
| الوصف: |
Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen. Among the top positive hits, we conducted an in-depth functional analysis on Pygopus family PHD finger 2 (PYGO2), located in the amplicon at 1q21.3. PYGO2 overexpression enhances primary tumor growth and local invasion to draining lymph nodes. Conversely, PYGO2 depletion inhibits prostate cancer cell invasion in vitro and progression of primary tumor and metastasis in vivo. In clinical samples, PYGO2 upregulation associated with higher Gleason score and metastasis to lymph nodes and bone. Silencing PYGO2 expression in patient-derived xenograft models impairs tumor progression. Finally, PYGO2 is necessary to enhance the transcriptional activation in response to ligand-induced Wnt/β-catenin signaling. Together, our results indicate that PYGO2 functions as a driver oncogene in the 1q21.3 amplicon and may serve as a potential prognostic biomarker and therapeutic target for metastatic prostate cancer. Significance: Amplification/overexpression of PYGO2 may serve as a biomarker for prostate cancer progression and metastasis. Cancer Res; 78(14); 3823–33. ©2018 AACR. |
| اللغة: |
English |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a9a0afec5c32f847412371998f2c4783
https://europepmc.org/articles/PMC6381393/ |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.doi.dedup.....a9a0afec5c32f847412371998f2c4783 |
| قاعدة البيانات: |
OpenAIRE |
