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Cancers
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Recent Advances in Carcinogenesis Transcription Factors: Biomarkers and Targeted Therapies
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Recent Advances in Carcinogenesis Transcription Factors: Biomarkers and Targeted Therapies

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

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 11243

Special Issue Editors

Prof. Dr. Ann M. Bode

E-Mail Website
Guest Editor
The Hormel Institute, University of Minnesota, Austin, MN 55912, USA
Interests: carcinogenesis; chemoprevention; transcription factors; cancer biomarkers; drug resistance
Prof. Dr. Rebecca Morris

E-Mail Website
Guest Editor
The Hormel Institute, University of Minnesota, Austin, MN 55912, USA
Interests: stem cells and cancer; keratinocyte stem cells; bone marrow stem cells; epithelial cancers
Dr. Tianshun Zhang

E-Mail Website
Guest Editor
The Hormel Institute, University of Minnesota, Austin, MN 55912, USA
Interests: targeted therapy; cancer biology; biomarkers; tumor microenvironment; molecular biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Recent Advances in Carcinogenesis Transcription Factors: Biomarkers and Targeted Therapies──How and when does a good cell go bad?

When a carcinogen-initiated cell goes bad, traditionally, the dogma is that it requires both a carcinogen and a tumor promoter. However, many cells are exposed to both agents but do not become cancerous. The transformation is believed to require a mutation or activation of a favorite oncogene but is also known to require a non-normal cell proliferation event or at least something beyond the normal day-to-day cell turnover. This “induced” proliferation event changes the entire phenotype of the initiated cell including the RNA and subsequent translated proteins. However, non-cancerous cells are not necessarily affected. Thus, transcription factors appear to be a major link between the mutation being established in subsequent rounds of cell cycle and the expression of the cancer phenotype. This Special Issue focuses on mutations in specific transcription factors that are considered to be most important in leading a bad cell to progress to cancer. This should include the coordinate regulation of cellular and tissue processes such as inflammation, hypoxia, and cell cycle/differentiation from a transcriptional point of view, as well as their regulation and coordination by enhancers and super enhancers and how they act as oncogenic drivers. Articles could also include how researchers jumped over the hurdle of determining how transcription factors could be druggable targets, which was proposed years ago, but not achieved until relatively recently.

Prof. Dr. Ann M. Bode
Prof. Dr. Rebecca Morris
Dr. Tianshun Zhang
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 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.

Keywords

  • transcription factor
  • oncogenic driver
  • targeted drug design
  • coordinate regulation of gene expression
  • super enhancers
  • carcinogenesis
  • targeted therapies
  • gene regulation
  • biomarkers

Published Papers (6 papers)

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Editorial

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5 pages, 216 KiB  
Editorial
Recent Advances in Carcinogenesis Transcription Factors: Biomarkers and Targeted Therapies
by Ann M. Bode and Tianshun Zhang
Cancers 2023, 15(19), 4673; https://doi.org/10.3390/cancers15194673 - 22 Sep 2023
Viewed by 962
Abstract
Carcinogenesis, the process by which normal cells transform into cancer cells, is complex and multifaceted [...] Full article
(This article belongs to the Special Issue Recent Advances in Carcinogenesis Transcription Factors: Biomarkers and Targeted Therapies)

Research

Jump to: Editorial, Review

19 pages, 24030 KiB  
Article
SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer
by Shan-Yueh Chang, Ti-Hui Wu, Yu-Lueng Shih, Ying-Chieh Chen, Her-Young Su, Chih-Feng Chian and Ya-Wen Lin
Cancers 2023, 15(8), 2207; https://doi.org/10.3390/cancers15082207 - 08 Apr 2023
Cited by 1 | Viewed by 1642
Abstract
The development of lung cancer is a complex process that involves many genetic and epigenetic changes. Sex-determining region Y (SRY)-box (SOX) genes encode a family of proteins that are involved in the regulation of embryonic development and cell fate determination. SOX1 is hypermethylated [...] Read more.
The development of lung cancer is a complex process that involves many genetic and epigenetic changes. Sex-determining region Y (SRY)-box (SOX) genes encode a family of proteins that are involved in the regulation of embryonic development and cell fate determination. SOX1 is hypermethylated in human cancers. However, the role of SOX1 in the development of lung cancer is unclear. We used quantitative methylation-specific polymerase chain reaction (MSP), quantitative reverse transcription polymerase chain reaction (RT–PCR) analysis, and web tools to confirm the frequent epigenetic silencing of SOX1 in lung cancer. Stable overexpression of SOX1 repressed cell proliferation, anchorage-independent growth, and invasion in vitro as well as cancer growth and metastasis in a xenograft mouse model. Knockdown of SOX1 by the withdrawal of doxycycline partly restored the malignant phenotype of inducible SOX1-expressing NSCLC cells. Next, we discovered the potential downstream pathways of SOX1 using RNA-seq analysis and identified HES1 as a direct target of SOX1 using chromatin immunoprecipitation (ChIP)-PCR. Furthermore, we performed phenotypic rescue experiments to prove that overexpression of HES1-FLAG in SOX1-expressing H1299 cells partly reversed the tumor-suppressive effect. Taken together, these data demonstrated that SOX1 acts as a tumor suppressor by directly inhibiting HES1 during the development of NSCLC. Full article
(This article belongs to the Special Issue Recent Advances in Carcinogenesis Transcription Factors: Biomarkers and Targeted Therapies)
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16 pages, 2712 KiB  
Article
Analysis of Primary Cilium Expression and Hedgehog Pathway Activation in Mesothelioma Throws Back Its Complex Biology
by Marcella Barbarino, Maria Bottaro, Laura Spagnoletti, Maria Margherita de Santi, Raffaella Guazzo, Chiara Defraia, Cosimo Custoza, Gabriella Serio, Francesco Iannelli, Matilde Pesetti, Raffaele Aiello, Diletta Rosati, Edoardo Zanfrini, Luca Luzzi, Cristiana Bellan and Antonio Giordano
Cancers 2022, 14(21), 5216; https://doi.org/10.3390/cancers14215216 - 25 Oct 2022
Cited by 3 | Viewed by 1879
Abstract
The primary cilium (PC) is a sensory organelle present on the cell surface, modulating the activity of many pathways. Dysfunctions in the PC lead to different pathologic conditions including cancer. Hedgehog signaling (Hh) is regulated by PC and the loss of its control [...] Read more.
The primary cilium (PC) is a sensory organelle present on the cell surface, modulating the activity of many pathways. Dysfunctions in the PC lead to different pathologic conditions including cancer. Hedgehog signaling (Hh) is regulated by PC and the loss of its control has been observed in many cancers, including mesothelioma. Malignant pleural mesothelioma (MPM) is a fatal cancer of the pleural membranes with poor therapeutic options. Recently, overexpression of the Hh transcriptional activator GL1 has been demonstrated to be associated with poor overall survival (OS) in MPM. However, unlike other cancers, the response to G-protein-coupled receptor smoothened (SMO)/Hh inhibitors is poor, mainly attributable to the lack of markers for patient stratification. For all these reasons, and in particular for the role of PC in the regulation of Hh, we investigated for the first time the status of PC in MPM tissues, demonstrating intra- and inter-heterogeneity in its expression. We also correlated the presence of PC with the activation of the Hh pathway, providing uncovered evidence of a PC-independent regulation of the Hh signaling in MPM. Our study contributes to the understanding MPM heterogeneity, thus helping to identify patients who might benefit from Hh inhibitors. Full article
(This article belongs to the Special Issue Recent Advances in Carcinogenesis Transcription Factors: Biomarkers and Targeted Therapies)
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19 pages, 2963 KiB  
Article
Hypoxia and ERα Transcriptional Crosstalk Is Associated with Endocrine Resistance in Breast Cancer
by Charly Jehanno, Pascale Le Goff, Denis Habauzit, Yann Le Page, Sylvain Lecomte, Estelle Lecluze, Frédéric Percevault, Stéphane Avner, Raphaël Métivier, Denis Michel and Gilles Flouriot
Cancers 2022, 14(19), 4934; https://doi.org/10.3390/cancers14194934 - 08 Oct 2022
Cited by 3 | Viewed by 1757
Abstract
Estrogen receptor-alpha (ERα) is the driving transcription factor in 70% of breast cancers and its activity is associated with hormone dependent tumor cell proliferation and survival. Given the recurrence of hormone resistant relapses, understanding the etiological factors fueling resistance is of major clinical [...] Read more.
Estrogen receptor-alpha (ERα) is the driving transcription factor in 70% of breast cancers and its activity is associated with hormone dependent tumor cell proliferation and survival. Given the recurrence of hormone resistant relapses, understanding the etiological factors fueling resistance is of major clinical interest. Hypoxia, a frequent feature of the solid tumor microenvironment, has been described to promote endocrine resistance by triggering ERα down-regulation in both in vitro and in vivo models. Yet, the consequences of hypoxia on ERα genomic activity remain largely elusive. In the present study, transcriptomic analysis shows that hypoxia regulates a fraction of ERα target genes, underlying an important regulatory overlap between hypoxic and estrogenic signaling. This gene expression reprogramming is associated with a massive reorganization of ERα cistrome, highlighted by a massive loss of ERα binding sites. Profiling of enhancer acetylation revealed a hormone independent enhancer activation at the vicinity of genes harboring hypoxia inducible factor (HIFα) binding sites, the major transcription factors governing hypoxic adaptation. This activation counterbalances the loss of ERα and sustains hormone-independent gene expression. We describe hypoxia in luminal ERα (+) breast cancer as a key factor interfering with endocrine therapies, associated with poor clinical prognosis in breast cancer patients. Full article
(This article belongs to the Special Issue Recent Advances in Carcinogenesis Transcription Factors: Biomarkers and Targeted Therapies)
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Review

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37 pages, 2265 KiB  
Review
Recent Advances in Transcription Factors Biomarkers and Targeted Therapies Focusing on Epithelial–Mesenchymal Transition
by Kai-Ting Chuang, Shyh-Shin Chiou and Shih-Hsien Hsu
Cancers 2023, 15(13), 3338; https://doi.org/10.3390/cancers15133338 - 25 Jun 2023
Cited by 4 | Viewed by 1392
Abstract
Transcription factors involve many proteins in the process of transactivating or transcribing (none-) encoded DNA to initiate and regulate downstream signals, such as RNA polymerase. Their unique characteristic is that they possess specific domains that bind to specific DNA element sequences called enhancer [...] Read more.
Transcription factors involve many proteins in the process of transactivating or transcribing (none-) encoded DNA to initiate and regulate downstream signals, such as RNA polymerase. Their unique characteristic is that they possess specific domains that bind to specific DNA element sequences called enhancer or promoter sequences. Epithelial–mesenchymal transition (EMT) is involved in cancer progression. Many dysregulated transcription factors—such as Myc, SNAIs, Twists, and ZEBs—are key drivers of tumor metastasis through EMT regulation. This review summarizes currently available evidence related to the oncogenic role of classified transcription factors in EMT editing and epigenetic regulation, clarifying the roles of the classified conserved transcription factor family involved in the EMT and how these factors could be used as therapeutic targets in future investigations. Full article
(This article belongs to the Special Issue Recent Advances in Carcinogenesis Transcription Factors: Biomarkers and Targeted Therapies)
28 pages, 2807 KiB  
Review
Advance of SOX Transcription Factors in Hepatocellular Carcinoma: From Role, Tumor Immune Relevance to Targeted Therapy
by Xiangyuan Luo, Xiaoyu Ji, Meng Xie, Tongyue Zhang, Yijun Wang, Mengyu Sun, Wenjie Huang and Limin Xia
Cancers 2022, 14(5), 1165; https://doi.org/10.3390/cancers14051165 - 24 Feb 2022
Cited by 8 | Viewed by 2876
Abstract
Sex determining region Y (SRY)-related high-mobility group (HMG) box (SOX) factors belong to an evolutionarily conserved family of transcription factors that play essential roles in cell fate decisions involving numerous developmental processes. In recent years, the significance of SOX factors in the initiation [...] Read more.
Sex determining region Y (SRY)-related high-mobility group (HMG) box (SOX) factors belong to an evolutionarily conserved family of transcription factors that play essential roles in cell fate decisions involving numerous developmental processes. In recent years, the significance of SOX factors in the initiation and progression of cancers has been gradually revealed, and they act as potential therapeutic targets for cancer. However, the research involving SOX factors is still preliminary, given that their effects in some leading-edge fields such as tumor immune microenvironment (TIME) remain obscure. More importantly, as a class of ‘undruggable’ molecules, targeting SOX factors still face considerable challenges in achieving clinical translation. Here, we mainly focus on the roles and regulatory mechanisms of SOX family members in hepatocellular carcinoma (HCC), one of the fatal human health burdens worldwide. We then detail the role of SOX members in remodeling TIME and analyze the association between SOX members and immune components in HCC for the first time. In addition, we emphasize several alternative strategies involved in the translational advances of SOX members in cancer. Finally, we discuss the alternative strategies of targeting SOX family for cancer and propose the opportunities and challenges they face based on the current accumulated studies and our understanding. Full article
(This article belongs to the Special Issue Recent Advances in Carcinogenesis Transcription Factors: Biomarkers and Targeted Therapies)
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