Transcription factors TEAD2 and E2A globally repress acetyl-CoA synthesis to promote tumorigenesis

Park, Su‐Jin; Mossmann, Dirk; Chen, Qian; Wang, Xueya; Dazert, Eva; Colombi, Marco; Schmidt, Alexander; Ryback, Brendan M; Ng, Charlotte K.Y.; Terracciano, Luigi; Heim, Markus H.; Hall, Michael N.

doi:10.1016/j.molcel.2022.10.027

Cited by 13 publications

(1 citation statement)

References 82 publications

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“…Furthermore, the TFs transcriptional enhanced associate domain 2 (TEAD2) and transcription factor E2-alpha (E2A) promote oncogenic dedifferentiation and proliferation in hepatocellular carcinoma (HCC). Mechanistically, TEAD2 and E2A repress acetyl-CoA synthesis to induce oncogenic dedifferentiation ( 19 ). Other examples include homeobox A5 ( 20 ) and SMAD4 ( 21 ) in colon cancer, Krüppel-like factor 5 in breast cancer ( 22 ) and microphthalmia-associated transcription factor in melanoma ( 23 ).…”

Section: Role Of Transcriptional Regulation Of Mrna In Cancer Cell Pl...mentioning

confidence: 99%

Epigenetic regulation of mRNA mediates the phenotypic plasticity of cancer cells during metastasis and therapeutic resistance (Review)

Zhang,

Liang,

Zhang

et al. 2023

Oncol Rep

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Plasticity, the ability of cancer cells to transition between differentiation states without genomic alterations, has been recognized as a major source of intratumoral heterogeneity. It has a crucial role in cancer metastasis and treatment resistance. Thus, targeting plasticity holds tremendous promise. However, the molecular mechanisms of plasticity in cancer cells remain poorly understood. Several studies found that mRNA, which acts as a bridge linking the genetic information of DNA and protein, has an important role in translating genotypes into phenotypes. The present review provided an overview of the regulation of cancer cell plasticity occurring via changes in the transcription and editing of mRNAs. The role of the transcriptional regulation of mRNA in cancer cell plasticity was discussed, including DNA-binding transcriptional factors, DNA methylation, histone modifications and enhancers. Furthermore, the role of mRNA editing in cancer cell plasticity was debated, including mRNA splicing and mRNA modification. In addition, the role of non-coding (nc)RNAs in cancer plasticity was expounded, including microRNAs, long intergenic ncRNAs and circular RNAs. Finally, different strategies for targeting cancer cell plasticity to overcome metastasis and therapeutic resistance in cancer were discussed.

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Section: Role Of Transcriptional Regulation Of Mrna In Cancer Cell Pl...mentioning

confidence: 99%

Epigenetic regulation of mRNA mediates the phenotypic plasticity of cancer cells during metastasis and therapeutic resistance (Review)

Zhang,

Liang,

Zhang

et al. 2023

Oncol Rep

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YAP/TAZ-TEAD activity promotes the malignant transformation of cervical intraepithelial neoplasia through enhancing the characteristics and Warburg effect of cancer stem cells

Li,

Yang

et al. 2024

Apoptosis

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A number of studies have confirmed that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)-transcriptional enhanced associate domain (TEAD) activity is the driver of cancer development. However, the role and mechanism of the YAP/TAZ-TEAD pathway in cervical intraepithelial neoplasia (CIN) remain to be clarified. Therefore, this study was designed to observe the effect of YAP/TAZ-TEAD activity on the development of CIN and provide new ideas for the diagnosis and treatment of CIN. Firstly, cervical tissues were collected from CIN patients in different stages [CIN grade 1 (CIN1) tissue, CIN grade 2/3 (CIN 2/3) and squamous cell carcinoma (SCC)] and healthy volunteers. Next, the expression levels of YAP, TAZ and TEAD in cervical tissues and cells were observed by immunohistochemistry, qRT-PCR and western blot. Besides, Z172 and Z183 cells were transfected with siRNA-YAP/TAZ (si-YAP/TAZ) and YAP/TAZ overexpression vector (YAP-5SA). Also, Z172 cells were co-transfected with YAP-5SA and si-TEAD2/4. Subsequently, the stemness characteristics, glycolysis level and malignant transformation of cells in each group were observed by sphere-formation assay, commercial kit, MTT, Transwell, scratch experiment, xenotransplantation and western blot.The expression of YAP, TAZ and TEAD increased significantly in cervical cancer tissue and cell line at the stage of CIN2/3 and SCC. When YAP/TAZ was knocked down, the stemness characteristics, glycolysis level and malignant transformation of cancer cells were notably inhibited; while activating YAP/TAZ exhibited a completely opposite result. In addition, activating YAP/TAZ and knocking down the TEAD expression at the same time significant weakened the effect of activated YAP/TAZ signal on precancerous cells and reduced inhibitory effect of knocking down TEAD alone. YAP/TAZ-TEAD signal activates the characteristics and Warburg effect of cancer stem cells, thereby promoting the malignant transformation of CIN.

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Regulation and targeting of SREBP-1 in hepatocellular carcinoma

Su,

Koeberle

2023

Cancer Metastasis Rev

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Hepatocellular carcinoma (HCC) is an increasing burden on global public health and is associated with enhanced lipogenesis, fatty acid uptake, and lipid metabolic reprogramming. De novo lipogenesis is under the control of the transcription factor sterol regulatory element-binding protein 1 (SREBP-1) and essentially contributes to HCC progression. Here, we summarize the current knowledge on the regulation of SREBP-1 isoforms in HCC based on cellular, animal, and clinical data. Specifically, we (i) address the overarching mechanisms for regulating SREBP-1 transcription, proteolytic processing, nuclear stability, and transactivation and (ii) critically discuss their impact on HCC, taking into account (iii) insights from pharmacological approaches. Emphasis is placed on cross-talk with the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt)-mechanistic target of rapamycin (mTOR) axis, AMP-activated protein kinase (AMPK), protein kinase A (PKA), and other kinases that directly phosphorylate SREBP-1; transcription factors, such as liver X receptor (LXR), peroxisome proliferator-activated receptors (PPARs), proliferator-activated receptor γ co-activator 1 (PGC-1), signal transducers and activators of transcription (STATs), and Myc; epigenetic mechanisms; post-translational modifications of SREBP-1; and SREBP-1-regulatory metabolites such as oxysterols and polyunsaturated fatty acids. By carefully scrutinizing the role of SREBP-1 in HCC development, progression, metastasis, and therapy resistance, we shed light on the potential of SREBP-1-targeting strategies in HCC prevention and treatment.

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Transcription factors TEAD2 and E2A globally repress acetyl-CoA synthesis to promote tumorigenesis

Cited by 13 publications

References 82 publications

Epigenetic regulation of mRNA mediates the phenotypic plasticity of cancer cells during metastasis and therapeutic resistance (Review)

Epigenetic regulation of mRNA mediates the phenotypic plasticity of cancer cells during metastasis and therapeutic resistance (Review)

YAP/TAZ-TEAD activity promotes the malignant transformation of cervical intraepithelial neoplasia through enhancing the characteristics and Warburg effect of cancer stem cells

Regulation and targeting of SREBP-1 in hepatocellular carcinoma

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