HBP1 is a new target of FOXO down-regulated by growth factor signaling

info:eu-repo/semantics/nonPublishe

HBP1: a new regulator of cell proliferation downstream of AKT and FOXO

info:eu-repo/semantics/nonPublishe

HBP1 is a new target of FOXO down-regulated by growth factor signaling

info:eu-repo/semantics/nonPublishe

HBP1 is a new FOXO target down-regulated by growth factor signaling

info:eu-repo/semantics/nonPublishe

The expression of the tumor suppressor HBP1 is down-regulated by growthfactors via the PI3K – PKB – FOXO pathway

Growth factors inactivate the Forkhead-box O (FOXO) transcription factors through phosphatidylinositol-3 kinase (PI3K) and protein kinase B (PKB). By comparing microarray data from multiple model systems, we identified the HMG-box protein 1 (HBP1) as a novel downstream target of this pathway. HBP1 mRNA was down-regulated by PDGF, FGF, PI3K and PKB, while it was up-regulated by FOXO factors. This observation was confirmed in human and murine fibroblasts as well as in cell lines derived from leukemia, breast adenocarcinoma and colon carcinoma. Bioinformatics analysis led to the identification of a conserved consensus FOXO-binding site in the HBP1 promoter. By luciferase activity assay and chromatin immunoprecipitation, we demonstrated that FOXO bound to this site and regulated the HBP1 promoter activity in a PI3K-dependent manner. Silencing of HBP1 by small-hairpin RNA (shRNA) increased human fibroblasts proliferation in response to growth factors, suggesting that HBP1 limits cell growth. Finally, by analyzing a transcriptomics data set from The Cancer Genome Atlas, we observed that HBP1 expression was lower in breast tumors that had lost FOXO expression. In conclusion, HBP1 is a novel target of the PI3K - FOXO pathway and controls cell proliferation in response to growth factor

Emerging roles of extracellular vesicles in the nervous system

Information exchange executed by extracellular vesicles, including exosomes, is a newly described form of intercellular communication important in the development and physiology of neural systems. These vesicles can be released from cells, are packed with information including signaling proteins and both coding and regulatory RNAs, and can be taken up by target cells, thereby facilitating the transfer of multilevel information. Recent studies demonstrate their critical role in physiological processes, including nerve regeneration, synaptic function, and behavior. These vesicles also have a sinister role in the propagation of toxic amyloid proteins in neurodegenerative conditions, including prion diseases and Alzheimer's and Parkinson's diseases, in inducing neuroinflammation by exchange of information between the neurons and glia, as well as in aiding tumor progression in the brain by subversion of normal cells. This article provides a summary of topics covered in a symposium and is not meant to be a comprehensive review of the subject

Corrigendum to “Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer” [Eur Urol 2023;83:313–17] (European Urology (2023) 83(4) (313–317), (S0302283822025386), (10.1016/j.eururo.2022.07.023))

The authors regret that the following statement regarding author contributions was missed: Kristan van der Vos is currently a Scientific Editor for Cell Reports Medicine, which is published by Elsevier. Dr van der Vos was not involved in the peer-review process or editorial discussions about this manuscript. The authors would like to apologise for any inconvenience caused.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Pattern Recognition and Bioinformatic

Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer

Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is recommended for patients with muscle-invasive bladder cancer (MIBC). It has been shown that somatic deleterious mutations in ERCC2, gain-of-function mutations in ERBB2, and alterations in ATM, RB1, and FANCC are correlated with pathological response to NAC in MIBC. The objective of this study was to validate these genomic biomarkers in pretreatment transurethral resection material from an independent retrospective cohort of 165 patients with MIBC who subsequently underwent NAC and radical surgery. Patients with ypT0/Tis/Ta/T1N0 disease after surgery were defined as responders. Somatic deleterious mutations in ERCC2 were found in nine of 68 (13%) evaluable responders and two of 95 (2%) evaluable nonresponders (p = 0.009; FDR = 0.03). No correlation was observed between response and alterations in ERBB2 or in ATM, RB1, or FANCC alone or in combination. In an exploratory analysis, no additional genomic alterations discriminated between responders and nonresponders to NAC. No further associations were identified between the aforementioned biomarkers and pathological complete response (ypT0N0) after surgery. In conclusion, we observed a positive association between deleterious mutations in ERCC2 and pathological response to NAC, but not overall survival or recurrence-free survival. Other previously reported genomic biomarkers were not validated. Patient summary: It is currently unknown which patients will respond to chemotherapy before definitive surgery for bladder cancer. Previous studies described several gene mutations in bladder cancer that correlated with chemotherapy response. This study confirmed that patients with bladder cancer with a mutation in the ERCC2 gene often respond to chemotherapy.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public. Corrigendum to “Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer” [Eur Urol 2023;83:313–17] (European Urology (2023) 83(4) (313–317), (S0302283822025386), (10.1016/j.eururo.2022.07.023)) The authors regret that the following statement regarding author contributions was missed: Kristan van der Vos is currently a Scientific Editor for Cell Reports Medicine, which is published by Elsevier. Dr van der Vos was not involved in the peer-review process or editorial discussions about this manuscript. The authors would like to apologise for any inconvenience caused.Pattern Recognition and Bioinformatic