TGF- β1 promotes epithelial-to-mesenchymal transition and stemness of prostate cancer cells by inducing PCBP1 degradation and alternative splicing of CD44.

TGF-β1 promotes epithelial-to-mesenchymal transition and stemness of prostate cancer cells by inducing PCBP1 degradation and alternative splicing of CD44. Cell Mol Life Sci. 2020 May 21;: Authors: Chen Q, Gu M, Cai ZK, Zhao H, Sun SC, Liu C, Zhan M, Chen YB, Wang Z Abstract CD44 is a marker of cancer stem cell (CSC) in many types of tumors. Alternative splicing of its 20 exons generates various CD44 isoforms that have different tissue specific expression and functions, including the CD44 standard isoform (CD44s) encoded by the constant exons and the CD44 variant isoforms (CD44v) with variant exon insertions. Switching between the CD44v and CD44s isoforms plays pivotal roles in tumor progression. Here we reported a novel mechanism of CD44 alternative splicing induced by TGF-β1 and its connection to enhanced epithelial-to-mesenchymal transition (EMT) and stemness in human prostate cancer cells. TGF-β1 treatment increased the expression of CD44s and N-cadherin while decreased the expression of CD44v and E-cadherin in DU-145 prostate cancer cells. Other EMT markers and cancer stem cell markers were also upregulated after TGF-β1 treatment. RNAi knockdown of CD44 reversed the phenotype, which could be rescued by overexpressing CD44s but not CD44v, indicating the alternatively spliced isoform CD44s mediated the activity of TGF-β1 treatment. Mechanistically, TGF-β1 treatment induced the phosphorylation, poly-ubiquitination, and degr...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
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The age-related decline of the immune system has several causes, but the involution of the thymus is an important one. The thymus is responsible for the production of mature T cells of the adaptive immune system, but the organ atrophies with age. The supply of new T cells falls off dramatically in later life, and without these reinforcements, the adaptive immune system becomes ever more populated with broken, misconfigured, senescent, exhausted, and outright harmful T cells. A few research groups and companies are investigating ways to restore the thymus, typically by provoking it to regrow. A number of approaches h...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
The objective is to start treating chronic diseases from the root and not the symptoms of the disease. As we are starting to enroll patients in "senolytics-clinical trials," it will be imperative to assess if senolysis efficiently targets the primary cause of disease or if it works best in combination with other drugs. Additional basic science research is required to address the fundamental role of senescent cells, especially in the established contexts of disease. Notes on Self-Experimentation with Sex Steroid Ablation for Regrowth of the Thymus https://www.fightaging.org/archives/2020/04/notes-on-se...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
I periodically publish thoughts on self-experiments that seem interesting and relevant to aging. Despite the influence of the quantified self movement, the broader self-experimentation community is largely terrible on matters of research, rigor, reporting, and safety. My motivation is to something to raise the bar on all of these items. For every discussion I've published on a particular self-experiment, there are half a dozen others sitting at some stage of research and interest. Over the past year or so, I've been on and off looking into sex steroid ablation as a mechanism for thymus regrowth. Since my company, Re...
Source: Fight Aging! - Category: Research Authors: Tags: Self-Experimentation Source Type: blogs
Authors: Assoun EN, Meyer AN, Jiang MY, Baird SM, Haas M, Donoghue DJ Abstract Prostate cancer affects hundreds of thousands of men and families throughout the world. Although chemotherapy, radiation, surgery, and androgen deprivation therapy are applied, these therapies do not cure metastatic prostate cancer. Patients treated by androgen deprivation often develop castration resistant prostate cancer which is incurable. Novel approaches of treatment are clearly necessary. We have previously shown that prostate cancer originates as a stem cell disease. A prostate cancer patient sample, #87, obtained from prostatecto...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
In this study, we intravenously administrated the young mitochondria into aged mice to evaluate whether energy production increase in aged tissues or age-related behaviors improved after the mitochondrial transplantation. The results showed that heterozygous mitochondrial DNA of both aged and young mouse coexisted in tissues of aged mice after mitochondrial administration, and meanwhile, ATP content in tissues increased while reactive oxygen species (ROS) level reduced. Besides, the mitotherapy significantly improved cognitive and motor performance of aged mice. Our study, at the first report in aged animals, not only prov...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The objective of this study was to identify differentially expressed microRNAs in these cell lines, which may be responsible for the EMT phenotype. Unsupervised hierarchical clustering confirmed that microRNA expression profiles are distinctly different between the two cell lines, with 119 miRNAs significantly increased and 81 microRNAs significantly decreased in ARCaPM cells as compared to ARCaPE. Further analysis revealed that many of the differentially expressed microRNAs belong to only a few microRNA families/clusters. Unsurprisingly, microRNAs in these clusters are co-expressed due to common promoters, which are known...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by high throughput sequencing Homo sapiens Source Type: research
by Shubham Tripathi, Priyanka Chakraborty, Herbert Levine, Mohit Kumar Jolly Epithelial-mesenchymal heterogeneity implies that cells within the same tumor can exhibit different phenotypes—epithelial, mesenchymal, or one or more hybrid epithelial-mesenchymal phenotypes. This behavior has been reported across cancer types, bothin vitro andin vivo, and implicated in multiple processes associated with metastatic aggressiveness including immune evasion, collective dissemination of tumor cells, and emergence of cancer cell subpopulations with stem cell-like properties. However, the ability of a population of cancer cells ...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research
Authors: Yeh Y, Guo Q, Connelly Z, Cheng S, Yang S, Prieto-Dominguez N, Yu X Abstract Metastatic or locally advanced prostate cancer (PCa) is typically treated with androgen deprivation therapy (ADT). Initially, PCa responds to the treatment and regresses. However, PCa almost always develops resistance to androgen deprivation and progresses to castrate-resistant prostate cancer (CRPCa), a currently incurable form of PCa. Wnt/β-Catenin signaling is frequently activated in late stage PCa and contributes to the development of therapy resistance. Although activating mutations in the Wnt/β-Catenin pathway are ...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Cancers, Vol. 11, Pages 1637: Galeterone and The Next Generation Galeterone Analogs, VNPP414 and VNPP433-3β Exert Potent Therapeutic Effects in Castration-/Drug-Resistant Prostate Cancer Preclinical Models In Vitro and In Vivo Cancers doi: 10.3390/cancers11111637 Authors: Andrew K. Kwegyir-Afful Senthilmurugan Ramalingam Vidya P. Ramamurthy Puranik Purushottamachar Francis N. Murigi Tadas S. Vasaitis Weiliang Huang Maureen A. Kane Yuji Zhang Nicholas Ambulos Sudhir Tiwari Pratima Srivastava Ivo P. Nnane Arif Hussain Yun Qiu David J. Weber Vincent C. O. Njar These studies compare...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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