Chiara Gorrini

University Health Network

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Louis Chesler

Institute of Cancer Research

Sumana Shrestha

Institute of Cancer Research

Karen Barker

Institute of Cancer Research

Qiong Gao

Institute of Cancer Research

Birgit Geoerger

Inserm

Cécile Pierre‐Eugène

Institut Curie

Alexandra Saint-Charles

Inserm

Deborah A. Tweddle

Newcastle University

Elizabeth R. Tucker

Institute of Cancer Research

Barbara Martins Da Costa

Institute of Cancer Research

Cooperative Institutions

University Health Network

Princess Margaret Cancer Centre

University of Toronto

Ontario Institute for Cancer Research

University of Milan

Cancer Genetics (United States)

Institut d'Investigació Biomédica de Bellvitge

Institute of Cancer Research

Cambridge University Press

Inserm

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

PTPN12 promotes resistance to oxidative stress and supports tumorigenesis by regulating FOXO signaling

Oncogene (2013)

Isaac S. Harris Heiko Blaser Juan Carlos Alvarez Moreno Aislinn E. Treloar Chiara Gorrini

10.1038/onc.2013.24

Cite

Citations (39)

E2F-Dependent Histone Acetylation and Recruitment of the Tip60 Acetyltransferase Complex to Chromatin in Late G₁

Molecular and Cellular Biology (2004)

Stefan Taubert Chiara Gorrini Scott R. Frank Tiziana Parisi Miriam Fuchs

E2F proteins can either activate or repress transcription.Following mitogenic stimulation, repressive E2F4-p130-histone deacetylase complexes dissociate from, while activating species (E2F1, -2, and -3) associate with, target promoters.Histones H3 and H4 simultaneously become hyperacetylated, but it remains unclear whether this is a prerequisite or a consequence of E2F binding.Here, we show that activating E2F species are required for hyperacetylation of target chromatin in human cells.Overexpression of a dominant-negative (DN) E2F1 mutant in serum-stimulated T98G cells blocked all E2F binding, H4 acetylation, and, albeit partially, H3 acetylation.Target gene activation and S-phase entry were also blocked by DN E2F1.Conversely, ectopic activation of E2F1 rapidly induced H3 and H4 acetylation, demonstrating a direct role for E2F in these events.E2F1 was previously shown to bind the histone acetyltransferases (HATs) p300/CBP and PCAF/GCN5.In our hands, ectopically expressed E2F1 also bound the unrelated HAT Tip60 and induced recruitment of five subunits of the Tip60 complex (Tip60, TRRAP, p400, Tip48, and Tip49) to target promoters in vivo.Moreover, E2F-dependent recruitment of Tip60 to chromatin occurred in late G 1 following serum stimulation.We speculate that the activities of multiple HAT complexes account for E2F-dependent acetylation, transcription, and S-phase entry.

E2F

Histone acetyltransferase

Histone H4

PCAF

10.1128/mcb.24.10.4546-4556.2004

Cite

Citations (207)

Figure S4 from Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models

Elizabeth R. Tucker Irène Jiménez Lindi Chen Angela Bellini Chiara Gorrini

GEMM sequencing data

10.1158/1078-0432.22489883.v1

Cite

Citations (0)

Figure S1 from Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models

Elizabeth R. Tucker Irène Jiménez Lindi Chen Angela Bellini Chiara Gorrini

Cell line and PDX genetics

10.1158/1078-0432.22489895

Cite

Citations (0)

BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival

The Journal of Experimental Medicine (2013)

Chiara Gorrini Pegah S. Baniasadi Isaac S. Harris Jennifer Silvester Satoshi Inoue

Oxidative stress plays an important role in cancer development and treatment. Recent data implicate the tumor suppressor BRCA1 in regulating oxidative stress, but the molecular mechanism and the impact in BRCA1-associated tumorigenesis remain unclear. Here, we show that BRCA1 regulates Nrf2-dependent antioxidant signaling by physically interacting with Nrf2 and promoting its stability and activation. BRCA1-deficient mouse primary mammary epithelial cells show low expression of Nrf2-regulated antioxidant enzymes and accumulate reactive oxygen species (ROS) that impair survival in vivo. Increased Nrf2 activation rescues survival and ROS levels in BRCA1-null cells. Interestingly, 53BP1 inactivation, which has been shown to alleviate several defects associated with BRCA1 loss, rescues survival of BRCA1-null cells without restoring ROS levels. We demonstrate that estrogen treatment partially restores Nrf2 levels in the absence of BRCA1. Our data suggest that Nrf2-regulated antioxidant response plays a crucial role in controlling survival downstream of BRCA1 loss. The ability of estrogen to induce Nrf2 posits an involvement of an estrogen-Nrf2 connection in BRCA1 tumor suppression. Lastly, BRCA1-mutated tumors retain a defective antioxidant response that increases the sensitivity to oxidative stress. In conclusion, the role of BRCA1 in regulating Nrf2 activity suggests important implications for both the etiology and treatment of BRCA1-related cancers.

10.1084/jem.20121337

Cite

Citations (257)

AhR controls redox homeostasis and shapes the tumor microenvironment in BRCA1-associated breast cancer

Proceedings of the National Academy of Sciences (2019)

Shawn P. Kubli C. Bassi Cecilia Roux Andrew Wakeham Christoph Göbl

Significance Basal-like/BRCA1-associated breast cancer (BC) is a very aggressive form of BC that frequently occurs in young women, with devastating effects. Since tailored therapies are lacking for this type of tumor, scientists and clinicians are searching for weaknesses that can be therapeutically exploited. Here we describe the role of the transcription factor aryl hydrocarbon receptor (AhR) in supporting BC growth by controlling reactive oxygen species (ROS) levels and the tumor-promoting features of the microenvironment. In BC cells, AhR activation mediates the link between intracellular ROS regulation and the protumorigenic functions of the surrounding immune system. We propose that tailored inhibition of AhR-regulated pathways can lead to BC eradication by pushing it beyond its ROS tolerance limit and depriving it of tumor-supporting immune cells.

Homeostasis

Tumor progression

10.1073/pnas.1815126116

Cite

Citations (99)

Role of Nek2 on centrosome duplication and aneuploidy in breast cancer cells

Oncogene (2013)

Paola Cappello Heiko Blaser Chiara Gorrini Dan Lin Andrew Elia

Tumor progression

10.1038/onc.2013.183

Cite

Citations (105)

MODL-02. A novelCre-conditionalcMYC-driven MB Group 3 transgenic mouse model shows traceable leptomeningeal dissemination.

Neuro-Oncology (2022)

Alaide Morcavallo Karen Barker Colin Kwok Jessica K.R. Boult Patricia Benites Goncalves da Silva

Abstract Medulloblastoma (MB), the most common embryonal tumour of the Central Nervous System, occurs in the cerebellum. Treatment regimens involve surgery, craniospinal radiotherapy, and chemotherapy. The greatest mortality is associated with disseminated disease, almost exclusively found in the leptomeningeal space. Unfortunately, knowledge about the aetiology of MB spread is limited and the need for kinder and efficacious therapy remains an unmet goal. Of the four molecular classified MB groups, Group3 (Gr3) MB presents with a high frequency of metastasis at diagnosis, with the worst overall survival. Gr3 MB tumours are dominated by primitive progenitor-like cells and cMYC deregulation; often, p53 deficiency is observed at relapse. To dissect the biology of primary and metastatic Gr3 MB, we have developed a new germline genetically engineered mouse model (GEMM), harbouring cMYC amplification in a Tamoxifen-inducible p53 functional background (Trp53ERTAM strain). A novel LSL-cMYC-CopGFP-Luciferase transgene was integrated into the Rosa-26 locus of the mouse genome. Transgenic mice were crossed with a strain expressing Cre recombinase under the Blbp promoter targeting embryonic neural progenitors, and subsequently bred to Trp53ERTAM mice. As result, the cMYC overexpression was sufficient to generate tumours. Tumour penetrance was observed in all the expected tumour bearing genotypes, with increased aggressiveness in a non-functional p53 background. Bioluminescence imaging demonstrated tumour onset in the brain and dissemination along the spinal cord. CopGFP positive tumour cells were isolated from primary and metastatic tumours. Pathological interrogation confirmed that tumours present large cell/anaplastic (LCA) histology. Analysis of preliminary transcriptional profiling data proved that tumours cluster with human Gr3 MB. Ongoing methylation profiling and multi-omics approaches will inform on the tumour cells of origin and clonal divergence of primary tumour versus metastasis. In conclusion, we have successfully developed a novel immunocompetent mouse model of metastatic Gr3 MB with which we can investigate therapeutic vulnerabilities of MB.

Cre recombinase

10.1093/neuonc/noac079.625

Cite

Citations (0)

Glutathione and Thioredoxin Antioxidant Pathways Synergize to Drive Cancer Initiation and Progression

Cancer Cell (2015)

Isaac S. Harris Aislinn E. Treloar Satoshi Inoue Masato Sasaki Chiara Gorrini

10.1016/j.ccell.2015.01.009

Cite

Citations (51)

Figure S3 from Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models

Elizabeth R. Tucker Irène Jiménez Lindi Chen Angela Bellini Chiara Gorrini

GEMM ALK inhibitor data

ALK inhibitor

10.1158/1078-0432.22494943

Cite

Citations (0)