Special Issue "HOX Genes in Cancer"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 March 2019)

Special Issue Editors

Guest Editor
Prof. Dr. Richard Morgan

Institute of Cancer Therapeutics, University of Bradford, Bradford, West Yorkshire BD7 1DP, UK
Website | E-Mail
Interests: HOX genes; prostate cancer; breast cancer; glioma; mesothelioma; acute myeloid leukemia; HXR9; PBX
Guest Editor
Prof. Dr. Keith D. Hunter

Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK
Website | E-Mail
Interests: HOX genes; head and neck cancer; oral pathology; microRNA
Guest Editor
Dr. Alex Thompson

School of Medicine, University of Nottingham, Nottingham, UK
Website | E-Mail
Interests: HOX genes; hematological malignancies; leukemia; HOXA; hematopoietic stem cells; connectivity mapping

Special Issue Information

Dear Colleagues,

The HOX genes are a family of transcription factors that play key roles in conferring cell and tissue identity during early development, but which are also frequently expressed at very high levels in a wide range of solid and hematological cancers. Over the last decade is has become apparent that the HOX genes can promote oncogenesis and the maintenance of a malignant phenotype, and are therefore potential therapeutic targets in cancer as well as biomarkers for diagnosis, prognosis, and patient stratification. This Special Issue, HOX Genes in Cancer, will provide a forum for the latest discoveries in this rapidly expanding field, and help make it accessible through reviews on key topics including the role of HOX genes in cancer stem cells, current progress on targeting HOX proteins in cancer, the cancer-specific functions of HOX genes, and the potential of HOX genes and their products as biomarkers.

Prof. Dr. Richard Morgan
Prof. Dr. Keith D. Hunter
Dr. Alex Thompson
Guest 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 papers will be 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 monthly 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 1800 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.

Keywords

  • HOX
  • PBX
  • cancer
  • HXR9
  • cancer stem cells
  • oncogenesis
  • biomarker

Published Papers (5 papers)

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Research

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Open AccessArticle Anatomic Origin of Osteochondrogenic Progenitors Impacts Sensitivity to EWS-FLI1-Induced Transformation
Cancers 2019, 11(3), 313; https://doi.org/10.3390/cancers11030313
Received: 14 February 2019 / Revised: 28 February 2019 / Accepted: 1 March 2019 / Published: 6 March 2019
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Abstract
Ewing sarcomas predominantly arise in pelvic and stylopod bones (i.e., femur and humerus), likely as a consequence of EWS-FLI1 oncogene-induced transformation of mesenchymal stem/progenitor cells (MSCs). MSCs located in the embryonic superficial zone cells (eSZ) of limbs express anatomically distinct posterior Hox genes. [...] Read more.
Ewing sarcomas predominantly arise in pelvic and stylopod bones (i.e., femur and humerus), likely as a consequence of EWS-FLI1 oncogene-induced transformation of mesenchymal stem/progenitor cells (MSCs). MSCs located in the embryonic superficial zone cells (eSZ) of limbs express anatomically distinct posterior Hox genes. Significantly, high expression of posterior HOXD genes, especially HOXD13, is a hallmark of Ewing sarcoma. These data drove our hypothesis that Hox genes in posterior skeleton MSCs contribute to Ewing sarcoma tumorigenesis. We isolated eSZ cells from stylopod and zeugopod (i.e., tibia/fibula, radius/ulna) bones, from wild-type and Hoxd13 mutant embryos, and tested the impact of EWS-FLI1 transduction on cell proliferation, gene expression, and tumorigenicity. Our data demonstrate that both stylopod and zeugopod eSZ cells tolerate EWS-FLI1 but that stylopod eSZ cells are relatively more susceptible, demonstrating changes in proliferation and gene expression consistent with initiation of malignant transformation. Significantly, loss of Hoxd13 had no impact, showing that it is dispensable for the initiation of EWS-FLI1-induced transformation in mouse MSCs. These findings show that MSCs from anatomically distinct sites are differentially susceptible to EWS-FLI1-induced transformation, supporting the premise that the dominant presentation of Ewing sarcoma in pelvic and stylopod bones is attributable to anatomically-defined differences in MSCs. Full article
(This article belongs to the Special Issue HOX Genes in Cancer)
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Review

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Open AccessReview The Role of HOX Transcription Factors in Cancer Predisposition and Progression
Cancers 2019, 11(4), 528; https://doi.org/10.3390/cancers11040528
Received: 18 March 2019 / Revised: 8 April 2019 / Accepted: 10 April 2019 / Published: 12 April 2019
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Abstract
Homeobox (HOX) transcription factors, encoded by a subset of homeodomain superfamily genes, play pivotal roles in many aspects of cellular physiology, embryonic development, and tissue homeostasis. Findings over the past decade have revealed that mutations in HOX genes can lead to increased cancer [...] Read more.
Homeobox (HOX) transcription factors, encoded by a subset of homeodomain superfamily genes, play pivotal roles in many aspects of cellular physiology, embryonic development, and tissue homeostasis. Findings over the past decade have revealed that mutations in HOX genes can lead to increased cancer predisposition, and HOX genes might mediate the effect of many other cancer susceptibility factors by recognizing or executing altered genetic information. Remarkably, several lines of evidence highlight the interplays between HOX transcription factors and cancer risk loci discovered by genome-wide association studies, thereby gaining molecular and biological insight into cancer etiology. In addition, deregulated HOX gene expression impacts various aspects of cancer progression, including tumor angiogenesis, cell autophagy, proliferation, apoptosis, tumor cell migration, and metabolism. In this review, we will discuss the fundamental roles of HOX genes in cancer susceptibility and progression, highlighting multiple molecular mechanisms of HOX involved gene misregulation, as well as their potential implications in clinical practice. Full article
(This article belongs to the Special Issue HOX Genes in Cancer)
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Open AccessReview A Case of Identity: HOX Genes in Normal and Cancer Stem Cells
Cancers 2019, 11(4), 512; https://doi.org/10.3390/cancers11040512
Received: 21 March 2019 / Revised: 8 April 2019 / Accepted: 9 April 2019 / Published: 10 April 2019
PDF Full-text (402 KB)
Abstract
Stem cells are undifferentiated cells that have the unique ability to self-renew and differentiate into many different cell types. Their function is controlled by core gene networks whose misregulation can result in aberrant stem cell function and defects of regeneration or neoplasia. HOX [...] Read more.
Stem cells are undifferentiated cells that have the unique ability to self-renew and differentiate into many different cell types. Their function is controlled by core gene networks whose misregulation can result in aberrant stem cell function and defects of regeneration or neoplasia. HOX genes are master regulators of cell identity and cell fate during embryonic development. They play a crucial role in embryonic stem cell differentiation into specific lineages and their expression is maintained in adult stem cells along differentiation hierarchies. Aberrant HOX gene expression is found in several cancers where they can function as either oncogenes by sustaining cell proliferation or tumor-suppressor genes by controlling cell differentiation. Emerging evidence shows that abnormal expression of HOX genes is involved in the transformation of adult stem cells into cancer stem cells. Cancer stem cells have been identified in most malignancies and proved to be responsible for cancer initiation, recurrence, and metastasis. In this review, we consider the role of HOX genes in normal and cancer stem cells and discuss how the modulation of HOX gene function could lead to the development of novel therapeutic strategies that target cancer stem cells to halt tumor initiation, progression, and resistance to treatment. Full article
(This article belongs to the Special Issue HOX Genes in Cancer)
Open AccessReview Kinase Regulation of HOX Transcription Factors
Cancers 2019, 11(4), 508; https://doi.org/10.3390/cancers11040508
Received: 12 March 2019 / Revised: 2 April 2019 / Accepted: 7 April 2019 / Published: 10 April 2019
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Abstract
The HOX genes are a group of homeodomain-containing transcription factors that play important regulatory roles in early development, including the establishment of cell and tissue identity. HOX expression is generally reduced in adult cells but is frequently re-established as an early event in [...] Read more.
The HOX genes are a group of homeodomain-containing transcription factors that play important regulatory roles in early development, including the establishment of cell and tissue identity. HOX expression is generally reduced in adult cells but is frequently re-established as an early event in tumour formation and supports an oncogenic phenotype. HOX transcription factors are also involved in cell cycle regulation and DNA repair, along with normal adult physiological process including stem cell renewal. There have been extensive studies on the mechanism by which HOX proteins regulate transcription, with particular emphasis on their interaction with cofactors such as Pre-B-cell Leukaemia Homeobox (PBX) and Myeloid Ecotropic Viral Integration Site 1 (MEIS). However, significantly less is known of how the activity of HOX proteins is regulated. There is growing evidence that phosphorylation may play an important role in this context, and in this review, we draw together a number of important studies published over the last 20 years, and discuss the relevance of phosphorylation in the regulation and function of HOX proteins in development, evolution, cell cycle regulation, and cancer. Full article
(This article belongs to the Special Issue HOX Genes in Cancer)
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Open AccessReview The Enigmatic HOX Genes: Can We Crack Their Code?
Cancers 2019, 11(3), 323; https://doi.org/10.3390/cancers11030323
Received: 2 February 2019 / Revised: 1 March 2019 / Accepted: 1 March 2019 / Published: 7 March 2019
Cited by 1 | PDF Full-text (1537 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Homeobox genes (HOX) are a large family of transcription factors that direct the formation of many body structures during early embryonic development. There are 39 genes in the subgroup of homeobox genes that constitute the human HOX gene family. Correct embryonic development of [...] Read more.
Homeobox genes (HOX) are a large family of transcription factors that direct the formation of many body structures during early embryonic development. There are 39 genes in the subgroup of homeobox genes that constitute the human HOX gene family. Correct embryonic development of flies and vertebrates is, in part, mediated by the unique and highly regulated expression pattern of the HOX genes. Disruptions in these fine-tuned regulatory mechanisms can lead to developmental problems and to human diseases such as cancer. Unfortunately, the molecular mechanisms of action of the HOX family of transcription factors are severely under-studied, likely due to idiosyncratic details of their structure, expression, and function. We suggest that a concerted and collaborative effort to identify interacting protein partners, produce genome-wide binding profiles, and develop HOX network inhibitors in a variety of human cell types will lead to a deeper understanding of human development and disease. Within, we review the technological challenges and possible approaches needed to achieve this goal. Full article
(This article belongs to the Special Issue HOX Genes in Cancer)
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