Phase separation in epigenetics and cancer stem cells

Xiao, Chanchan; Wu, Guohui; Chen, Pengfei; Gao, Lijuan; Chen, Guobing; Zhang, Hongyi

doi:10.3389/fonc.2022.922604

Cited by 6 publications

(2 citation statements)

References 120 publications

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“…It has been hypothesized that phase separation promotes the tumorigenicity of CSCs through ubiquitination. For example, the mutation of speckle-type POZ protein (SPOP), which prevents the recruitment of ligase substrates, facilitates the accumulation of proto-oncoproteins and triggers the phase separation of SPOP, maintaining the ubiquitination of ubiquitin-dependent proteins [52]. OCT4 is known as a master transcription factor for somatic cell reprogramming.…”

Section: Phase Separationmentioning

confidence: 99%

Hematopoietic Stem Cell: Regulation and Nutritional Intervention

et al. 2023

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Hematopoietic stem cells (HSCs) are crucial for the life maintenance of bio-organisms. However, the mechanism of HSC regulation is intricate. Studies have shown that there are various factors, either intrinsically or extrinsically, that shape the profile of HSCs. This review systematically summarizes the intrinsic factors (i.e., RNA-binding protein, modulators in epigenetics and enhancer–promotor-mediated transcription) that are reported to play a pivotal role in the function of HSCs, therapies for bone marrow transplantation, and the relationship between HSCs and autoimmune diseases. It also demonstrates the current studies on the effects of high-fat diets and nutrients (i.e., vitamins, amino acids, probiotics and prebiotics) on regulating HSCs, providing a deep insight into the future HSC research.

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Section: Phase Separationmentioning

confidence: 99%

Hematopoietic Stem Cell: Regulation and Nutritional Intervention

et al. 2023

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“…Changes in transcriptional control mechanisms are associated with the progression of cancer and cancer stem cells, leading to treatment-resistance, recurrence and metastasis ( 88 ). This section focus on the transcriptional networks involved in the progression of prostate cancer (PC).…”

Section: Activation and Emergence Of Distinctive Transcription Factor...mentioning

confidence: 99%

Targeting phase separation on enhancers induced by transcription factor complex formations as a new strategy for treating drug-resistant cancers

Takayama

Inoue

2022

Front. Oncol.

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The limited options for treating patients with drug-resistant cancers have emphasized the need to identify alternative treatment targets. Tumor cells have large super-enhancers (SEs) in the vicinity of important oncogenes for activation. The physical process of liquid-liquid phase separation (LLPS) contributes to the assembly of several membrane-less organelles in mammalian cells. Intrinsically disordered regions (IDRs) of proteins induce LLPS formation by developing condensates. It was discovered that key transcription factors (TFs) undergo LLPS in SEs. In addition, TFs play critical roles in the epigenetic and genetic regulation of cancer progression. Recently, we revealed the essential role of disease-specific TF collaboration changes in advanced prostate cancer (PC). OCT4 confers epigenetic changes by promoting complex formation with TFs, such as Forkhead box protein A1 (FOXA1), androgen receptor (AR) and Nuclear respiratory factor 1 (NRF1), inducing PC progression. It was demonstrated that TF collaboration through LLPS underlying transcriptional activation contributes to cancer aggressiveness and drug resistance. Moreover, the disruption of TF-mediated LLPS inhibited treatment-resistant PC tumor growth. Therefore, we propose that repression of TF collaborations involved in the LLPS of SEs could be a promising strategy for advanced cancer therapy. In this article, we summarize recent evidence highlighting the formation of LLPS on enhancers as a potent therapeutic target in advanced cancers.

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