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Cancers
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Inhibitor of Growth (ING) Genes
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Inhibitor of Growth (ING) Genes

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 22192

Special Issue Editor

Dr. Rémy Pedeux

E-Mail Website
Guest Editor
INSERM U1242 COSS laboratory, Universit é de Rennes-1, 35042 Rennes, France
Interests: INhibitor or Growth genes, tumor suppressor genes, dna damage, dna repair, therapies; lung cancer; cell death; apoptosis; senescence; cell cycle

Special Issue Information

Dear Colleagues,

ING1 (Growth Inhibitor 1) was identified more than 20 years ago as a tumor suppressor gene. In the years that followed, it was revealed that ING1 belonged to a family of highly conserved proteins, both structurally and functionally, from yeast to human. In humans, there are 5 ING genes. Reports have shown that loss of expression of ING proteins is common in many tumor types. KO mice for ING1 or ING2 spontaneously develop tumors. Functionally, ING proteins are all involved in acetylation or deacetylation complexes and in chromatin remodeling. ING proteins have a PHD (Plant HomeoDomain) motif that has a strong affinity for the histone brand H3K4me3. Consequently, ING proteins are responsible for the targeting of histone acetylase or histone deacetylase complex to specific chromatin sites. ING proteins are involved in important functions such as cell cycle control, apoptosis and cellular senescence. The regulation of their functions remains little known; however, sumoylation of ING proteins appears to play an important role.

In this special issue, we will publish original journals and research that provide new insights into the role of ING genes in cancer. This will go from the mechanisms responsible for their loss of expression in human tumors to their functions in suppressive tumor signaling pathways and how these functions are regulated. Finally, information on how they can be used as markers or therapeutically targeted will be welcome.

Dr. Rémy Pedeux
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (6 papers)

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Review

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12 pages, 1916 KiB  
Review
ING Proteins: Tumour Suppressors or Oncoproteins
by Karine Jacquet and Olivier Binda
Cancers 2021, 13(9), 2110; https://doi.org/10.3390/cancers13092110 - 27 Apr 2021
Cited by 8 | Viewed by 2066
Abstract
The INhibitor of Growth family was defined in the mid-1990s by the identification of a tumour suppressor, ING1, and subsequent expansion of the family based essentially on sequence similarities. However, later work and more recent investigations demonstrate that at least a few ING [...] Read more.
The INhibitor of Growth family was defined in the mid-1990s by the identification of a tumour suppressor, ING1, and subsequent expansion of the family based essentially on sequence similarities. However, later work and more recent investigations demonstrate that at least a few ING proteins are actually required for normal proliferation of eukaryotic cells, from yeast to human. ING proteins are also part of a larger family of chromatin-associated factors marked by a plant homeodomain (PHD), which mediates interactions with methylated lysine residues. Herein, we discuss the role of ING proteins and their various roles in chromatin signalling in the context of cancer development and progression. Full article
(This article belongs to the Special Issue Inhibitor of Growth (ING) Genes)
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19 pages, 1935 KiB  
Review
Focus-ING on DNA Integrity: Implication of ING Proteins in Cell Cycle Regulation and DNA Repair Modulation
by Jérôme Archambeau, Alice Blondel and Rémy Pedeux
Cancers 2020, 12(1), 58; https://doi.org/10.3390/cancers12010058 - 24 Dec 2019
Cited by 13 | Viewed by 4875
Abstract
The ING family of tumor suppressor genes is composed of five members (ING1-5) involved in cell cycle regulation, DNA damage response, apoptosis and senescence. All ING proteins belong to various HAT or HDAC complexes and participate in chromatin remodeling that is essential for [...] Read more.
The ING family of tumor suppressor genes is composed of five members (ING1-5) involved in cell cycle regulation, DNA damage response, apoptosis and senescence. All ING proteins belong to various HAT or HDAC complexes and participate in chromatin remodeling that is essential for genomic stability and signaling pathways. The gatekeeper functions of the INGs are well described by their role in the negative regulation of the cell cycle, notably by modulating the stability of p53 or the p300 HAT activity. However, the caretaker functions are described only for ING1, ING2 and ING3. This is due to their involvement in DNA repair such as ING1 that participates not only in NERs after UV-induced damage, but also in DSB repair in which ING2 and ING3 are required for accumulation of ATM, 53BP1 and BRCA1 near the lesion and for the subsequent repair. This review summarizes evidence of the critical roles of ING proteins in cell cycle regulation and DNA repair to maintain genomic stability. Full article
(This article belongs to the Special Issue Inhibitor of Growth (ING) Genes)
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17 pages, 1175 KiB  
Review
Biological Functions of the ING Proteins
by Arthur Dantas, Buthaina Al Shueili, Yang Yang, Arash Nabbi, Dieter Fink and Karl Riabowol
Cancers 2019, 11(11), 1817; https://doi.org/10.3390/cancers11111817 - 19 Nov 2019
Cited by 28 | Viewed by 4096
Abstract
The proteins belonging to the inhibitor of growth (ING) family of proteins serve as epigenetic readers of the H3K4Me3 histone mark of active gene transcription and target histone acetyltransferase (HAT) or histone deacetylase (HDAC) protein complexes, in order to alter local chromatin structure. [...] Read more.
The proteins belonging to the inhibitor of growth (ING) family of proteins serve as epigenetic readers of the H3K4Me3 histone mark of active gene transcription and target histone acetyltransferase (HAT) or histone deacetylase (HDAC) protein complexes, in order to alter local chromatin structure. These multidomain adaptor proteins interact with numerous other proteins to facilitate their localization and the regulation of numerous biochemical pathways that impinge upon biological functions. Knockout of some of the ING genes in murine models by various groups has verified their status as tumor suppressors, with ING1 knockout resulting in the formation of large clear-cell B-lymphomas and ING2 knockout increasing the frequency of ameloblastomas, among other phenotypic effects. ING4 knockout strongly affects innate immunity and angiogenesis, and INGs1, ING2, and ING4 have been reported to affect apoptosis in different cellular models. Although ING3 and ING5 knockouts have yet to be published, preliminary reports indicate that ING3 knockout results in embryonic lethality and that ING5 knockout may have postpartum effects on stem cell maintenance. In this review, we compile the known information on the domains of the INGs and the effects of altering ING protein expression, to better understand the functions of this adaptor protein family and its possible uses for targeted cancer therapy. Full article
(This article belongs to the Special Issue Inhibitor of Growth (ING) Genes)
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14 pages, 1234 KiB  
Review
Exploiting ING2 Epigenetic Modulation as a Therapeutic Opportunity for Non-Small Cell Lung Cancer
by Alice Blondel, Amine Benberghout, Rémy Pedeux and Charles Ricordel
Cancers 2019, 11(10), 1601; https://doi.org/10.3390/cancers11101601 - 21 Oct 2019
Cited by 8 | Viewed by 4067
Abstract
Non-small cell lung cancer (NSCLC) has been the leading cause of cancer-related death worldwide, over the last few decades. Survival remains extremely poor in the metastatic setting and, consequently, innovative therapeutic strategies are urgently needed. Inhibitor of Growth Gene 2 (ING2) is a [...] Read more.
Non-small cell lung cancer (NSCLC) has been the leading cause of cancer-related death worldwide, over the last few decades. Survival remains extremely poor in the metastatic setting and, consequently, innovative therapeutic strategies are urgently needed. Inhibitor of Growth Gene 2 (ING2) is a core component of the mSin3A/Histone deacetylases complex (HDAC), which controls the chromatin acetylation status and modulates gene transcription. This gene has been characterized as a tumor suppressor gene and its status in cancer has been scarcely explored. In this review, we focused on ING2 and other mSin3A/HDAC member statuses in NSCLC. Taking advantage of existing public databases and known pharmacological properties of HDAC inhibitors, finally, we proposed a therapeutic model based on an ING2 biomarker-guided strategy. Full article
(This article belongs to the Special Issue Inhibitor of Growth (ING) Genes)
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12 pages, 236 KiB  
Review
The Biological and Clinical Relevance of Inhibitor of Growth (ING) Genes in Non-Small Cell Lung Cancer
by Elisabeth Smolle, Nicole Fink-Neuboeck, Joerg Lindenmann, Freyja Smolle-Juettner and Martin Pichler
Cancers 2019, 11(8), 1118; https://doi.org/10.3390/cancers11081118 - 06 Aug 2019
Cited by 6 | Viewed by 2584
Abstract
Carcinogenic mutations allow cells to escape governing mechanisms that commonly inhibit uncontrolled cell proliferation and maintain tightly regulated homeostasis between cell death and survival. Members of the inhibition of growth (ING) family act as tumor suppressors, governing cell cycle, apoptosis and cellular senescence. [...] Read more.
Carcinogenic mutations allow cells to escape governing mechanisms that commonly inhibit uncontrolled cell proliferation and maintain tightly regulated homeostasis between cell death and survival. Members of the inhibition of growth (ING) family act as tumor suppressors, governing cell cycle, apoptosis and cellular senescence. The molecular mechanism of action of ING genes, as well as their anchor points in pathways commonly linked to malignant transformation of cells, have been studied with respect to a variety of cancer specimens. This review of the current literature focuses specifically on the action mode of ING family members in lung cancer. We have summarized data from in vitro and in vivo studies, highlighting the effects of varying levels of ING expression in cancer cells. Based on the increasing insight into the function of these proteins, the use of ING family members as clinically useful biomarkers for lung cancer detection and prognosis will probably become routine in everyday clinical practice. Full article
(This article belongs to the Special Issue Inhibitor of Growth (ING) Genes)

Other

Jump to: Review

13 pages, 1796 KiB  
Brief Report
Loss of Ing3 Expression Results in Growth Retardation and Embryonic Death
by Dieter Fink, Tienyin Yau, Arash Nabbi, Bettina Wagner, Christine Wagner, Shiting Misaki Hu, Viktor Lang, Stephan Handschuh, Karl Riabowol and Thomas Rülicke
Cancers 2020, 12(1), 80; https://doi.org/10.3390/cancers12010080 - 29 Dec 2019
Cited by 12 | Viewed by 3892
Abstract
The ING3 candidate tumour suppressor belongs to a family of histone modifying proteins involved in regulating cell proliferation, senescence, apoptosis, chromatin remodeling, and DNA repair. It is a stoichiometric member of the minimal NuA4 histone acetyl transferase (HAT) complex consisting of EAF6, EPC1, [...] Read more.
The ING3 candidate tumour suppressor belongs to a family of histone modifying proteins involved in regulating cell proliferation, senescence, apoptosis, chromatin remodeling, and DNA repair. It is a stoichiometric member of the minimal NuA4 histone acetyl transferase (HAT) complex consisting of EAF6, EPC1, ING3, and TIP60. This complex is responsible for the transcription of an essential cascade of genes involved in embryonic development and in tumour suppression. ING3 has been linked to head and neck and hepatocellular cancers, although its status as a tumour suppressor has not been well established. Recent studies suggest a pro-metastasis role in prostate cancer progression. Here, we describe a transgenic mouse strain with insertional mutation of an UbC-mCherry expression cassette into the endogenous Ing3 locus, resulting in the disruption of ING3 protein expression. Homozygous mutants are embryonically lethal, display growth retardation, and severe developmental disorders. At embryonic day (E) 10.5, the last time point viable homozygous embryos were found, they were approximately half the size of heterozygous mice that develop normally. µCT analysis revealed a developmental defect in neural tube closure, resulting in the failure of formation of closed primary brain vesicles in homozygous mid-gestation embryos. This is consistent with high ING3 expression levels in the embryonic brains of heterozygous and wild type mice and its lack in homozygous mutant embryos that show a lack of ectodermal differentiation. Our data provide direct evidence that ING3 is an essential factor for normal embryonic development and that it plays a fundamental role in prenatal brain formation. Full article
(This article belongs to the Special Issue Inhibitor of Growth (ING) Genes)
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