Determination of AP-2 Transcription Factors Role in Carcinogenesis

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Microenvironment".

Deadline for manuscript submissions: closed (18 July 2023) | Viewed by 4775

Special Issue Editors

Department of Functional Genomics, Medical University of Lodz, 90-752 Lodz, Poland
Interests: carcinogenesis; gene expression regulation; molecular mechanisms; transcription factors
Special Issues, Collections and Topics in MDPI journals
Department of Experimental Surgery, Medical University of Lodz, 90-136 Lodz, Poland
Interests: functional genomics; high-throughput sequencing; in silico; transcription factors
Department of Experimental Surgery, Medical University of Lodz, 90-136 Lodz, Poland
Interests: cancer; neurology; in vitro; genetics; transcription factors

Special Issue Information

Dear Colleagues,

In homeostatic conditions, the transcription factors from the Activating enhancer-binding Protein 2 (AP-2) family regulate embryogenesis, ensuring the correct formation of limbs, eyes or facial features. Thus, they are mainly expressed during the early stages of development; however, their altered functionality was also found to play a crucial role in carcinogenesis, influencing the prognosis of cancer patients. The fact that each AP-2 transcription factor has a different impact on a given tumor, makes this complex field worth investigating. In this Special Issue, we sincerely encourage you to submit your prominent cancer research related to the AP-2 family to the wider scientific community. It is intended to collect the articles being literature reviews or papers presented in silico, in vitro or in vivo research.

Dr. Elżbieta Janina Płuciennik
Guest Editor

Damian Kołat
Żaneta Kałuzińska-Kołat
Guest Editor Assistants

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Keywords

  • AP-2
  • TFAP2 genes
  • carcinogenesis
  • cancer
  • transcription factors

Published Papers (2 papers)

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Research

21 pages, 5701 KiB  
Article
Differential Expression of AP-2 Transcription Factors Family in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma—A Bioinformatics Study
by Dagmara Szmajda-Krygier, Adrian Krygier, Marta Żebrowska-Nawrocka, Jacek Pietrzak, Rafał Świechowski, Agnieszka Wosiak, Agnieszka Jeleń and Ewa Balcerczak
Cells 2023, 12(4), 667; https://doi.org/10.3390/cells12040667 - 20 Feb 2023
Cited by 1 | Viewed by 1766
Abstract
Members of the activator protein 2 (AP-2) transcription factor (TF) family are known to play a role in both physiological processes and cancer development. The family comprises five DNA-binding proteins encoded by the TFAP2A to TFAP2E genes. Numerous scientific reports describe differential expression [...] Read more.
Members of the activator protein 2 (AP-2) transcription factor (TF) family are known to play a role in both physiological processes and cancer development. The family comprises five DNA-binding proteins encoded by the TFAP2A to TFAP2E genes. Numerous scientific reports describe differential expression of these TF and their genes in various types of cancer, identifying among them a potential oncogene or suppressor like TFAP2A or TFAP2C. Other reports suggest their influence on disease development and progression, as well as response to treatment. Not all members of this AP-2 family have been comprehensively studied thus far. The aim of the present article is to gather and discuss knowledge available in bioinformatics databases regarding all five members of this family and to differentiate them in relation to the two most common lung cancer subtypes: adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). In addition, to assess the difference in levels depending on a number of clinicopathological factors, the impact on patient survival and interactions with tumor-infiltrating immune cells. This article may help to identify the target for further original research that may contribute to the discovery of new diagnostic biomarkers and define the molecular differences between LUAD and LUSC, which may affect the therapy effectiveness improvement and longer survival. Full article
(This article belongs to the Special Issue Determination of AP-2 Transcription Factors Role in Carcinogenesis)
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25 pages, 19569 KiB  
Article
AP-2δ Is the Most Relevant Target of AP-2 Family-Focused Cancer Therapy and Affects Genome Organization
by Damian Kołat, Lin-Yong Zhao, Mateusz Kciuk, Elżbieta Płuciennik and Żaneta Kałuzińska-Kołat
Cells 2022, 11(24), 4124; https://doi.org/10.3390/cells11244124 - 19 Dec 2022
Cited by 3 | Viewed by 2168
Abstract
Formerly hailed as “undruggable” proteins, transcription factors (TFs) are now under investigation for targeted therapy. In cancer, this may alter, inter alia, immune evasion or replicative immortality, which are implicated in genome organization, a process that accompanies multi-step tumorigenesis and which frequently develops [...] Read more.
Formerly hailed as “undruggable” proteins, transcription factors (TFs) are now under investigation for targeted therapy. In cancer, this may alter, inter alia, immune evasion or replicative immortality, which are implicated in genome organization, a process that accompanies multi-step tumorigenesis and which frequently develops in a non-random manner. Still, targeting-related research on some TFs is scarce, e.g., among AP-2 proteins, which are known for their altered functionality in cancer and prognostic importance. Using public repositories, bioinformatics tools, and RNA-seq data, the present study examined the ligandability of all AP-2 members, selecting the best one, which was investigated in terms of mutations, targets, co-activators, correlated genes, and impact on genome organization. AP-2 proteins were found to have the conserved “TF_AP-2” domain, but manifested different binding characteristics and evolution. Among them, AP-2δ has not only the highest number of post-translational modifications and extended strands but also contains a specific histidine-rich region and cleft that can receive a ligand. Uterine, colon, lung, and stomach tumors are most susceptible to AP-2δ mutations, which also co-depend with cancer hallmark genes and drug targets. Considering AP-2δ targets, some of them were located proximally in the spatial genome or served as co-factors of the genes regulated by AP-2δ. Correlation and functional analyses suggested that AP-2δ affects various processes, including genome organization, via its targets; this has been eventually verified in lung adenocarcinoma using expression and immunohistochemistry data of chromosomal conformation-related genes. In conclusion, AP-2δ affects chromosomal conformation and is the most appropriate target for cancer therapy focused on the AP-2 family. Full article
(This article belongs to the Special Issue Determination of AP-2 Transcription Factors Role in Carcinogenesis)
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