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Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Transcription factor profiling shows new ways towards new treatment options of cutaneous T cell lymphomas
1Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. Udo.Doebbeling@usz.ch
Abstract:
Most oncogenes encode activators of transcription factors or transcription factors themselves. Transcription factors that are induced by growth stimuli are, in contrast to transcription factors that regulate house keeping genes, tightly regulated and only active, when a stimulus (e.g. cytokines or other growth factors) is given. Examples of such transcription factors are members of the jun, fos, myc, NFkB and STAT gene families. In cancer cells this regulation is interrupted, resulting in constitutive activities of transcription factors that are normally silent. This in turn results in the increased expression of target genes that are necessary for growth and protection from apoptosis. Since inducible transcription factors are activated by specific pathways, the identification of unusual constitutively active transcription factors also identifies the involved signal transduction pathway. Inhibitors of the components of these pathways may be effective anti-cancer agents, as they interrupt the abnormal signalling and in cancer cells. We applied this strategy for two forms of cutaneous T cell lymphomas and identified several groups of agents that may be the prototypes of new drugs to fight these diseases.
Insights
Most oncogenes involve transcription factors. In cancer, these factors become constitutively active, driving tumor growth and apoptosis resistance. Targeting these aberrant pathways offers new anti-cancer drug strategies, particularly for cutaneous T cell lymphomas.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Most oncogenes encode transcription factor activators.
- Inducible transcription factors are tightly regulated by growth stimuli.
- Cancer cells exhibit dysregulated transcription factor activity, leading to uncontrolled growth and apoptosis resistance.
Purpose of the Study:
- To investigate the role of transcription factors in cancer.
- To identify aberrant signaling pathways in cutaneous T cell lymphomas.
- To explore potential therapeutic targets for cancer treatment.
Main Methods:
- Analysis of oncogene-encoded transcription factors.
- Identification of constitutively active transcription factors in cancer cells.
- Application of pathway analysis to cutaneous T cell lymphomas.
Main Results:
- Dysregulated transcription factors are crucial in cancer progression.
- Specific signaling pathways were identified in cutaneous T cell lymphomas.
- Several classes of agents were identified as potential anti-cancer drugs.
Conclusions:
- Aberrant transcription factor activity is a hallmark of cancer.
- Targeting dysregulated pathways can inhibit cancer cell growth and survival.
- The identified agents show promise as novel therapeutics for cutaneous T cell lymphomas.
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General Transcription Factors

