What is a CancerTranscription Factor?
Published on : 01-06-2023
The transcription factor NF-kB controls many distinct genes that have a broad range of activities, including immunological and inflammatory responses NF-kB is activated in response to suitable cellular stimulation, most often pathogen or stress-related signals
Transcription factors (TFs) are the key players in tumor genesis and development Their exceptional versatility and efficacy make them appealing prognostic and therapeutic targets
TFs are known to have DNA binding and transactivation domains Many of them also interact with proteins that are downstream of signaling cascades
It is worth noting that NF-kB activation is often connected with the upregulation of anti-apoptotic genes, hence giving cell survival strategies to endure physiological stress. Furthermore, NF-kB generates cytokines and adhesion molecules essential for the innate immune response to inflammation
Inflammation, in general, and NF-kB, in particular, have a dual function in cancer development
On the one hand, inflammatory stimuli drive cancer cells to produce aberrant NF-kB target gene clusters (see related page), enabling them to grow and increase uncontrolled.
On the other hand, NF-kB may be constitutively active in certain cancers and perform pro-tumorogenic tasks such as enhanced cell proliferation, apoptosis resistance, angiogenesis, and invasion This is one of the primary reasons why many individuals with chronic inflammatory disorders are at a higher risk of cancer.
TP53 is one of the most critical transcription factors in cancer, and it is involved in every facet of tumor development and survival. Tumors' capacity to react to therapy and spread to other body regions is included
Wild-type p53 slows cell growth after DNA damage until the damaged cells are healed. A TP53 gene mutation causes the protein to become hyperactive, allowing cells to multiply in ways that lead to cancer.
When DNA damage is too severe to repair, TP53 is also responsible for signaling cell death (apoptosis). This can slow the development of malignant cells while activating the immune system to fight malignancies
C-Myc is a transcription factor that controls several genes in cellular programs essential for normal and malignant cell development and proliferation. These are examples of the cell cycle, self-renewal, survival, metabolism, protein and ribosome biogenesis, and differentiation
This is because c-Myc may attach to E boxes and activate genes, including hundreds of genes with a c-Myc binding site (Figure 3) The overwhelming majority of c-Myc-regulated gene expression occurs due to coordinated alterations in various cellular processes.
C-Myc is mainly inactive in resting cells It is, nevertheless, significantly increased in proliferating cells, leading to cancer and cell transformation.
C-Myc is critical for tumor cell evasion of the host immune response and its oncogenic function This is due to the ability of c-Myc to influence innate and adaptive immune regulatory cytokines like CD47 and PD-L1, which are essential for tumor initiation and development These cytokines are downregulated when c-Myc is inactivated, which may result in an immunological response to the tumor This, in turn, may result in cellular senescence of residual cancer cells, a halt in angiogenesis, and tumor removal
Pparg is a transcription factor that controls a variety of physiological functions Its primary function is to stimulate and decrease lipid metabolite expression, but it also plays a role in immunomodulation.
The PPARg gene is located on chromosome 3p25 and is composed of 9 exons (exon A1-2, exon B-D, and exons 1-6). Various PPARg mRNA and protein isoforms are produced through alternative promoter and mRNAsplicing
Pparg is expressed in various cell types, including immune cells and cancer cells, and it plays a function in the genesis of cancer It may work by "traditional" transactivation or activating Cdk6, a cyclin-dependent kinase, to cause phosphorylation of the c-MYC protein, which NF-kB controls Its capacity to increase cell proliferation and susceptibility to chemotherapy has also been linked to cancer development
