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Role of Tumour Suppressor Gene Products of Common Fragile Sites in Human Diseases

Total Cost €


EC-Contrib. €






 TSGPs-of-CFSs project word cloud

Explore the words cloud of the TSGPs-of-CFSs project. It provides you a very rough idea of what is the project "TSGPs-of-CFSs" about.

fragile    subjected    mutations    progression    causes    chromosomal    suggested    wwox    beta    suggest    expanded    lab    outcome    opposing    mouse    tools    cancer    preneoplastic    cytogenetics    genes    play    determined    molecular    selectively    damage    human    vivo    rearrangements    tumours    genome    instability    cycle    stems    vitro    confirmatory    gene    regions    span    replication    dominate    transformation    stability    conventional    observations    alterations    driver    sequences    first    pancreatic    cell    passenger    sites    residing    precancerous    diseases    cfss    apoptosis    tsgps    tumour    cells    counter    genetic    context    prone    regarding    functions    roles    genomic    correlated    fhit    tackle    school    dna    examine    argument    deletions    thought    lesions    tsgs    transgenic    stress    suppressor    question    diabetes    collateral    breakage    involvement    ing    metabolic    views    material    protection    common    t2d    unselected   

Project "TSGPs-of-CFSs" data sheet

The following table provides information about the project.


Organization address
postcode: 91904

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Israel [IL]
 Project website
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-05-01   to  2021-04-30


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

Common fragile sites (CFSs) are large chromosomal regions identified by conventional cytogenetics as sequences prone to breakage in cells subjected to replication stress. The interest in CFSs stems from their key role in DNA damage, resulting in chromosomal rearrangements. The instability of CFSs was correlated with genome instability in precancerous lesions and during tumour progression. Two opposing views dominate the discussion regarding the role of CFSs. One school of thought suggested that genomic instability during cancer progression causes collateral damage to genes residing within CFSs, such as WWOX and FHIT. These genes are proposed to be unselected ‘‘passenger’’ mutations. The counter argument is that deletions and other genomic alterations in CFSs occur early in cancer development. Cancer cells with deletions in genes that span CFSs are then selectively expanded due to loss of tumour suppressor functions such as protection of genome stability, coordination of cell cycle or apoptosis. Recent observations from my lab clearly suggest that gene products from CFSs play driver roles in cancer transformation. Moreover, we have evidence for the involvement of DNA damage and Wwox in pancreatic β-cells in the context of diabetes. Here, I propose to investigate the role of tumour suppressor gene products (TSGPs) of CFSs in human diseases. Three approaches will be taken to tackle this question. First, molecular functions of TSGPs of CFSs will be determined using state-of-the-art genetic tools in vitro. Second, novel transgenic mouse tools will be used to study CFSs and their associated TSGs in preneoplastic lesions and tumours in vivo, with confirmatory studies in human material. Third, we will examine the potential involvement of CFSs and their TSGPs in type-2 diabetes (T2D). The expected outcome is a detailed molecular understanding of CFSs and their associated TSGPs in genomic instability as well as their roles in cancer and metabolic diseases.


year authors and title journal last update
List of publications.
2019 Suhaib K. Abdeen, Rami I. Aqeilan
Decoding the link between WWOX and p53 in aggressive breast cancer
published pages: 1177-1186, ISSN: 1538-4101, DOI: 10.1080/15384101.2019.1616998
Cell Cycle 18/11 2019-09-04
2019 Teresa Druck, Douglas G. Cheung, Dongju Park, Francesco Trapasso, Flavia Pichiorri, Marco Gaspari, Tiziana Palumbo, Rami I. Aqeilan, Eugenio Gaudio, Hiroshi Okumura, Rodolfo Iuliano, Cinzia Raso, Kari Green, Kay Huebner, Carlo M. Croce
Fhit–Fdxr interaction in the mitochondria: modulation of reactive oxygen species generation and apoptosis in cancer cells
published pages: , ISSN: 2041-4889, DOI: 10.1038/s41419-019-1414-7
Cell Death & Disease 10/3 2019-09-04
2019 Saleh Khawaled, Sung Suk Suh, Suhaib K. Abdeen, Jonathan Monin, Rosario Distefano, Giovanni Nigita, Carlo M. Croce, Rami I. Aqeilan
WWOX Inhibits Metastasis of Triple-Negative Breast Cancer Cells via Modulation of miRNAs
published pages: 1784-1798, ISSN: 0008-5472, DOI: 10.1158/0008-5472.can-18-0614
Cancer Research 79/8 2019-09-04
2019 Muhannad Abu-Remaileh, Monther Abu-Remaileh, Rania Akkawi, Ibrahim Knani, Shiran Udi, Micheal E. Pacold, Joseph Tam, Rami I. Aqeilan
WWOX somatic ablation in skeletal muscles alters glucose metabolism
published pages: 132-140, ISSN: 2212-8778, DOI: 10.1016/j.molmet.2019.01.010
Molecular Metabolism 22 2019-09-04
2016 Idit Hazan, Thomas G. Hofmann, Rami I. Aqeilan
Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response
published pages: e1006436, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1006436
PLOS Genetics 12/12 2019-06-18
2018 Suhaib K. Abdeen, Uri Ben-David, Aya Shweiki, Bella Maly, Rami I. Aqeilan
Somatic loss of WWOX is associated with TP53 perturbation in basal-like breast cancer
published pages: , ISSN: 2041-4889, DOI: 10.1038/s41419-018-0896-z
Cell Death & Disease 9/8 2019-05-27
2018 Muhannad Abu-Remaileh, Abed Khalaileh, Eli Pikarsky, Rami I. Aqeilan
WWOX controls hepatic HIF1α to suppress hepatocyte proliferation and neoplasia
published pages: , ISSN: 2041-4889, DOI: 10.1038/s41419-018-0510-4
Cell Death & Disease 9/5 2019-05-27
2018 Mayur Tanna, Rami I. Aqeilan
Modeling WWOX Loss of Function in vivo: What Have We Learned?
published pages: , ISSN: 2234-943X, DOI: 10.3389/fonc.2018.00420
Frontiers in Oncology 8 2019-05-27

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