Transcription Factors: The Fulcrum Between Cell Development and Carcinogenesis

Higher eukaryotic development is a complex and tightly regulated process, whereby transcription factors (TFs) play a key role in controlling the gene regulatory networks. Dysregulation of these regulatory networks has also been associated with carcinogenesis. Transcription factors are key enablers of cancer stemness, which support the maintenance and function of cancer stem cells that are believed to act as seeds for cancer initiation, progression and metastasis, and treatment resistance. One key area of research is to understand how these factors interact and collaborate to define cellular fate during embryogenesis as well as during tumor development. This review focuses on understanding the role of TFs in cell development and cancer. The molecular mechanisms of cell fate decision are of key importance in efforts towards developing better protocols for directed differentiation of cells in research and medicine. We also discuss the dysregulation of TFs and their role in cancer progression and metastasis, exploring TF networks as direct or indirect targets for therapeutic intervention, as well as specific TFs’ potential as biomarkers for predicting and monitoring treatment responses.

• Publication year

  2021

• Venue

  Frontiers in Oncology

• Publication date

  2021-06-14

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fonc.2021.681377PMID 34195082PMCID 8236851
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Sall1 plays pivotal roles for lens fiber cell differentiation in mouse.

  2019influential reference
• Distinct structural classes of activating FOXA1 alterations in advanced prostate cancer

  2019cited by this paper
• Upregulated forkhead-box A3 elevates the expression of forkhead-box A1 and forkhead-box A2 to promote metastasis in esophageal cancer.

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• miR-181a-2* expression is different amongst carcinomas from the colorectal serrated route.

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  2018cited by this paper
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  2018cited by this paper
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  2018cited by this paper
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  2018cited by this paper
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• FOXA1 inhibits prostate cancer neuroendocrine differentiation

  2017cited by this paper
• The Emerging Roles of Forkhead Box (FOX) Proteins in Osteosarcoma

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• Characterisation of GATA3 expression in invasive breast cancer: differences in histological subtypes and immunohistochemically defined molecular subtypes

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  2017cited by this paper
• GATA3 expression and its relationship with clinicopathological parameters in invasive breast carcinomas.

  2017cited by this paper
• On a FOX hunt: functions of FOX transcriptional regulators in bladder cancer

  2017cited by this paper
• Krüppel-like factor 4 (KLF4): What we currently know.

  2017cited by this paper
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  2017cited by this paper
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• Peroxisome proliferator-activated receptor δ promotes colonic inflammation and tumor growth

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