Abstract
Cancer is a multi-step process and requires constitutive expression/activation of transcription factors (TFs) for growth and survival. Many of the TFs reported so far are critical for carcinogenesis. These include pro-inflammatory TFs, hypoxia-inducible factors (HIFs), cell proliferation and epithelial–mesenchymal transition (EMT)-controlling TFs, pluripotency TFs upregulated in cancer stem-like cells, and the nuclear receptors (NRs). Some of those, including HIFs, Myc, ETS-1, and β-catenin, are multifunctional and may regulate multiple other TFs involved in various pro-oncogenic events, including proliferation, survival, metabolism, invasion, and metastasis. High expression of some TFs is also correlated with poor prognosis and chemoresistance, constituting a significant challenge in cancer treatment. Considering the pivotal role of TFs in cancer, there is an urgent need to develop strategies targeting them. Targeting TFs, in combination with other chemotherapeutics, could emerge as a better strategy to target cancer. So far, targeting NRs have shown promising results in improving survival. In this review, we provide a comprehensive overview of the TFs that play a central role in cancer progression, which could be potential therapeutic candidates for developing specific inhibitors. Here, we also discuss the efforts made to target some of those TFs, including NRs.
Highlights
Cancer is defined as the uncontrolled proliferation of cells caused primarily by dysregulation of the proto-oncogenes and/or tumor-suppressor genes
Cancer cells highly depend on the constitutive expression of transcription factors (TFs) to support their growth and survival
Increasing knowledge of the mechanism of action and regulatory networks of the TFs has led to a better understanding of their roles in cancer and other diseases
Summary
Cancer is defined as the uncontrolled proliferation of cells caused primarily by dysregulation of the proto-oncogenes and/or tumor-suppressor genes. Tumor-suppressor genes, the negative regulators of the cell cycle, may become inactivated due to “loss of function” mutations or deletion in one of the alleles. The tumor-suppressor TFs are the negative regulators of cell cycle and are involved in DNA repair and apoptosis. Loss of function of tumor-suppressor TFs leads to uncontrolled cell division and progression of cancer [2]. Wilms tumor-suppressor TF suppressed the transcription of growth-promoting genes and was found complexity, a recentin study hascancer identified paradoxical functions through database searches to be less expressed breast [11].genes. Were for TFs which can have both oncogenic and tumor-suppressor functions in different cancers [12]. We discuss some of the crucial opened new possibilities to utilize TFs as cancer drug targets.
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