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State-of-the-Art Molecular Oncology in Israel
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State-of-the-Art Molecular Oncology in Israel

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 6040

Special Issue Editors

Prof. Dr. Rachel Bar-Shavit

E-Mail Website
Collection Editor
Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel
Interests: G-protein coupled receptors (GPCRs) involvement in tumor biology; the role of protease-activated receptors (PARs) oncogenes in canmcer
Special Issues, Collections and Topics in MDPI journals
Dr. Aviad Zick

E-Mail Website
Collection Editor
Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel
Interests: translating DNA characterization to oncological care; identifying germline mutations in patient population; describing the clinical aspects characterizing somatic DNA mutations and DNA amplicon structure; describing novel genes in repair pathways

Special Issue Information

Dear Colleagues,

The field of molecular Oncology is greatly benefited due to advances in bioinformatics tools and sequencing technologies. Information on DNA methylation, gene expression and copy number alterations altogether provide a tipoff as to the complexity of human cancer.  Nonetheless, merely providing a list of genomic variations is the first stage in the long endeavor for translating this information to cancer therapeutics.

DNA characterization as part of the oncological clinical care and research today is one of the leading aspects in the Oncologist research. Available capabilities in the tool-box utilize a panel of sequencing applications among of which are  massive parallel -, whole exome - and whole genome sequencing. These  are  routinely applied now on clinical samples including plasma and formalin fixed paraffin embedded tissue. In parallel, enhanced know-hows in bioinformatics serve to better extract the pertinent data for a research question.

Immunotherapy has changed the landscape of cancer therapy. The discovery of cancer immune checkpoints have practically reformed the war against cancer. Research in cancer immunotherapy has greatly enhanced our understanding in harnessing  the human immune response.

Although genomic, transcriptomic and immunohistochemical analyses of tumor tissues have immensely contributed to early-detection diagnostic and provide a wealth of information,  understanding the molecular mechanism of cancer stem cells is in the frontline. Translational means to eradicate cancer stem cells are highly warranted and the focus of current efforts in Oncology.

Prof. Dr. Rachel Bar-Shavit
Dr. Aviad Zick
Collection Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Keywords

  • oncogenes
  • Wnt/beta-catenin pathway
  • cell-free DNA
  • genetics
  • immunotherapy

Published Papers (2 papers)

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18 pages, 3505 KiB  
Article
PAR-Induced Harnessing of EZH2 to β-Catenin: Implications for Colorectal Cancer
by Shoshana Sedley, Jeetendra Kumar Nag, Tatyana Rudina and Rachel Bar-Shavit
Int. J. Mol. Sci. 2022, 23(15), 8758; https://doi.org/10.3390/ijms23158758 - 6 Aug 2022
Cited by 2 | Viewed by 1637
Abstract
G-protein-coupled receptors (GPCRs) are involved in a wide array of physiological and disease functions, yet knowledge of their role in colon cancer stem cell maintenance is still lacking. In addition, the molecular mechanisms underlying GPCR-induced post-translational signaling regulation are poorly understood. Here, we [...] Read more.
G-protein-coupled receptors (GPCRs) are involved in a wide array of physiological and disease functions, yet knowledge of their role in colon cancer stem cell maintenance is still lacking. In addition, the molecular mechanisms underlying GPCR-induced post-translational signaling regulation are poorly understood. Here, we find that protease-activated receptor 4 (PAR4) unexpectedly acts as a potent oncogene, inducing β-catenin stability and transcriptional activity. Both PAR4 and PAR2 are able to drive the association of methyltransferase EZH2 with β-catenin, culminating in β-catenin methylation. This methylation on a lysine residue at the N-terminal portion of β-catenin suppresses the ubiquitination of β-catenin, thereby promoting PAR-induced β-catenin stability and transcriptional activity. Indeed, EZH2 is found to be directly correlated with high PAR4-driven tumors, and is abundantly expressed in large tumors, whereas very little to almost none is expressed in small tumors. A truncated form of β-catenin, ∆N133β-catenin, devoid of lysine, as well as serine/threonine residues, exhibits low levels of β-catenin and a markedly reduced transcriptional activity following PAR4 activation, in contrast to wt β-catenin. Our study demonstrates the importance of β-catenin lysine methylation in terms of its sustained expression and function. Taken together, we reveal that PAR-induced post-transcriptional regulation of β-catenin is centrally involved in colon cancer. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Israel)
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Review

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14 pages, 1624 KiB  
Review
Lysyl Oxidase Family Enzymes and Their Role in Tumor Progression
by Tanya Liburkin-Dan, Shira Toledano and Gera Neufeld
Int. J. Mol. Sci. 2022, 23(11), 6249; https://doi.org/10.3390/ijms23116249 - 2 Jun 2022
Cited by 21 | Viewed by 3651
Abstract
The five genes of the lysyl oxidase family encode enzymes that covalently cross-link components of the extracellular matrix, such as various types of collagen and elastin, and, thus, promote the stabilization of extracellular matrixes. Several of these genes, in particular lysyl oxidase (LOX) [...] Read more.
The five genes of the lysyl oxidase family encode enzymes that covalently cross-link components of the extracellular matrix, such as various types of collagen and elastin, and, thus, promote the stabilization of extracellular matrixes. Several of these genes, in particular lysyl oxidase (LOX) and lysyl oxidase like-2 (LOXL2) were identified as genes that are upregulated by hypoxia, and promote tumor cells invasion and metastasis. Here, we focus on the description of the diverse molecular mechanisms by which the various lysyl oxidases affect tumor progression. We also describe attempts that have been made, and are still on-going, that focus on the development of efficient lysyl oxidase inhibitors for the treatment of various forms of cancer, and of diseases associated with abnormal fibrosis. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Israel)
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