Cancers, Vol. 12, Pages 660: Aurora Kinase A-YBX1 Synergy Fuels Aggressive Oncogenic Phenotypes and Chemoresistance in Castration-Resistant Prostate Cancer

Cancers, Vol. 12, Pages 660: Aurora Kinase A-YBX1 Synergy Fuels Aggressive Oncogenic Phenotypes and Chemoresistance in Castration-Resistant Prostate Cancer Cancers doi: 10.3390/cancers12030660 Authors: Kumar Nikhil Asif Raza Hanan S. Haymour Benjamin V. Flueckiger Jiachong Chu Kavita Shah Multifunctional protein YBX1 upregulation promotes castration-resistant prostate cancer (CRPC). However, YBX1 protein abundance, but not its DNA status or mRNA levels, predicts CRPC recurrence, although the mechanism remains unknown. Similarly, the mechanism by which YBX1 regulates androgen receptor (AR) signaling remains unclear. We uncovered the first molecular mechanism of YBX1 upregulation at a post-translational level. YBX1 was identified as an Aurora Kinase-A (AURKA) substrate using a chemical screen. AURKA phosphorylates YBX1 at two key residues, which stabilizes it and promotes its nuclear translocation. YBX1 reciprocates and stabilizes AURKA, thereby initiating a synergistic loop. Notably, phospho-resistant YBX1 is dominant-negative and fully inhibits epithelial to mesenchymal transition, chemoresistance, drug-resistance and tumorigenesis in vivo. Unexpectedly, we further observed that YBX1 upregulates AR post-translationally by preventing its ubiquitylation, but not by increasing its transcription as reported before. Uncovering YBX1-mediated AR stabilization is highly significant due to AR’s critical role in both androgen-sensitive prostate cancer and CR...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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In conclusion, the results of the present study demonstrated that nuclear ID‑SDC‑1 localization was associated with SNAIL expression in PCa cell lines. PMID: 32124938 [PubMed - as supplied by publisher]
Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Tags: Int J Mol Med Source Type: research
Authors: Krumbholz M, Agaimy A, Stoehr R, Burger M, Wach S, Taubert H, Wullich B, Hartmann A, Metzler M Abstract There is increasing interest in the use of cell-free circulating tumor DNA (ctDNA) as a serum marker for therapy assessment in prostate cancer patients. Prostate cancer is characterized by relatively low numbers of mutations, and, in contrast to many other common epithelial cancers, commercially available single nucleotide mutation assays for quantification of ctDNA are insufficient for therapy assessment in this disease. However, prostate cancer shares some similarity with translocation-affected mesench...
Source: Disease Markers - Category: Laboratory Medicine Tags: Dis Markers Source Type: research
wa Ogunwobi Prostate cancer (PCa) is the most common non-cutaneous cancer and second leading cause of cancer-related death for men in the United States. The nonprotein coding gene locus plasmacytoma variant translocation 1 (PVT1) is located at 8q24 and is dysregulated in different cancers. PVT1 gives rise to several alternatively spliced transcripts and microRNAs. There are at least twelve exons of PVT1, which make separate transcripts, and likely have different functions. Here, we demonstrate that PVT1 exon 9 is significantly overexpressed in PCa tissues in comparison to normal prostate tissues. Both transient and ...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article 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
AbstractPurposePrimary breast and prostate cancers can be cured, but metastatic disease cannot. Identifying cell factors that predict metastatic potential could guide both prognosis and treatment.MethodsWe used Cell-SELEX to screen an RNA aptamer library for differential binding to prostate cancer cell lines with high vs. low metastatic potential. Mass spectroscopy, immunoblot, and immunohistochemistry were used to identify and validate aptamer targets. Aptamer properties were tested in vitro, in xenograft models, and in clinical biopsies. Gene expression datasets were queried for target associations in cancer.ResultsWe id...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
In this study we adopted an all-in-one method. Primers designed according to the two gRNA sequences and the tracRNA-U6 vector sequences were used to produce a gRNA1-tracRNA-U6-gRNA2 fragment. Then the proper fragment was ligated into the lentiCRISPRv2 vector and verified by sequencing. Lentiviral Packaging and Stable Cell Line Screening The constructed eukaryotic expression vector and gene knockdown vector were transfected into the 293T cells with the packaging plasmids psPAX2 and pMD2.G using Lipofectamine 2000 (Thermo Fisher, Massachusetts, USA). The lentivirus was harvested 48 h after transfection, and the lentivirus ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Lei Liu1,2,3, Lin Zhang1,2, Shuo Zhao4, Xu-Yang Zhao1,2, Peng-Xiang Min4, Ya-Dong Ma4, Yue-Yuan Wang4, Yan Chen1,2, Si-Jie Tang4, Yu-Jie Zhang2,4, Jun Du2,4 and Luo Gu2,4* 1Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China 2Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China 3Department of Physiology, Xuzhou Medical University, Xuzhou, China 4Department of Physiology, Nanjing Medical University, Nanjing, China Tumor cell migration is a critical step...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Zhi-Chao Hu1,2,3†, Zu-Cheng Luo1,2,3†, Bing-Jie Jiang1,2,3†, Xin Fu1,2,3, Jiang-Wei Xuan1,2,3, Xiao-Bin Li1,2,3, Yu-Jie Bian1,2,3, Wen-Fei Ni1,2,3* and Ji-Xin Xue1,2,3* 1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China 2The Second School of Medicine, Wenzhou Medical University, Wenzhou, China 3Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, China Osteoarthritis (OA), defined as a long-term progressive joint disease, is characterized by cartilage impairment and ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Hepatoma-Derived Growth Factor and DDX5 Promote Carcinogenesis and Progression of Endometrial Cancer by Activating β-Catenin Chunhua Liu1†, Lijing Wang1†, Qingping Jiang2†, Junyi Zhang3†, Litong Zhu1, Li Lin1, Huiping Jiang1, Dan Lin1, Yanyi Xiao1, Weiyi Fang1,3 and Suiqun Guo1* 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China 2Department of Pathology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 3Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guang...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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