Inside the stemness engine: Mechanistic links between deregulated transcription factors and stemness in cancer

Ervin, Egle-Helene; French, Rhiannon; Chang, Chao-Hui; Pauklin, Siim

doi:10.1016/j.semcancer.2022.11.001

Cited by 24 publications

(24 citation statements)

References 554 publications

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“…We can notice that Oct4 IDRs contain a high density of Prolines, which are not directly detectable in the present 1 HN-detected experiments, even though most of the 13 Ca, 13 Cb and resonances were characterized via HNCAB and HNCO experiments. We have shown previously that the 13 C-detected experiments 13 Ca 13 CO permitted to observe all these Pro residues in Oct4(aa1-145) [99], whose chemical shifts were those of random coil peptides.…”

Section: Structural Characterization Of the N-and C-terminal Regions ...contrasting

confidence: 57%

“…The 2D 1 H-15 N HSQC NMR spectra showed crosspeaks in the spectra region where random coil peptides resonances are usually found (Figure 1). We assigned the backbone NMR signals of 1 HN, 15 N, 13 Ca, 13 Cb, 13 CO for both segments, which permitted to calculate experimentally derived secondary structure propensities from the 13 Ca and 13 Cb chemical shifts. We did not find any sign of a stable secondary structure, the highest a-helical propensities reaching about 25 % in short stretches of about 5 consecutive amino acids.…”

Section: Structural Characterization Of the N-and C-terminal Regions ...mentioning

confidence: 99%

“…These bind to enhancer sequences, and thus activate or repress, or even "bookmark" during mitosis, a wealth of genes related to pluripotency or cell differentiation [4][5][6][7][8][9]. Consistently, their misregulation correlates with cancer malignancy and stemness [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 98%

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Structural characterization of stem cell factors Oct4, Sox2, Nanog and Esrrb disordered domains, and a method to identify their phospho-dependent binding partners

Bouguechtouli

Ghouil

Alik

et al. 2023

Preprint

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The combined expression of a handful of pluripotency transcription factors (PluriTFs) in somatic cells can generate induced pluripotent stem cells (iPSCs). Here, we report the structural characterization of disordered regions contained in four important PluriTFs, namely Oct4, Sox2, Nanog and Esrrb. Moreover, many post-translational modifications (PTMs) have been detected on PluriTFs, whose roles are not yet characterized. To help in their study, we also present a method i) to produce well-characterized phosphorylation states of PluriTFs, using NMR analysis, and ii) to use them for pull-downs in stem cell extracts analyzed by quantitative proteomics to identify of Sox2 binders.

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Section: Structural Characterization Of the N-and C-terminal Regions ...contrasting

confidence: 57%

Section: Structural Characterization Of the N-and C-terminal Regions ...mentioning

confidence: 99%

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Structural characterization of stem cell factors Oct4, Sox2, Nanog and Esrrb disordered domains, and a method to identify their phospho-dependent binding partners

Bouguechtouli

Ghouil

Alik

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…However, K-Ras activation is not mandatory for the survival of PDAC cells; therefore, alternative mechanisms for YAP induction exist in pancreatic cancer [ 63 ]. In general, YAP and TAZ in tumours can be up-regulated by a wide scope of mechanisms, including amplification of the YAP gene, inactivation of the Hippo pathway, activating K-Ras mutations or interaction with other molecular pathways, including Notch, Wnt or TGFβ [ 66 ].…”

Section: Signalling Pathways In Pdac Cscmentioning

confidence: 99%

“…Upregulation of YAP and TAZ in different cancers (oesophageal squamous cell carcinoma, head and neck squamous cell carcinoma bladder cancer, lung cancer) is associated with increased expression of stemness markers CD44, CD133, SOX2, SOX9, Nanog, ALDH, higher chemoresistance, higher expression of multi drug resistance efflux transport ATP-binding cassette transporter protein ABCG2 and more active colony formation [ 66 ]. Similarly, in pancreatic cancer, nuclear translocation of YAP, induced by hepatocyte growth factor secreted by pancreatic stellate cells, increased the tumour sphere formation ability as well as the expression of stemness markers Nanog, OCT-4 and SOX-2 [ 67 ].…”

Section: Signalling Pathways In Pdac Cscmentioning

confidence: 99%

Cancer Stem Cells in Pancreatic Ductal Adenocarcinoma

Bubin

Uljanovs

Štrumfa

2023

IJMS

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The first discovery of cancer stem cells (CSCs) in leukaemia triggered active research on stemness in neoplastic tissues. CSCs represent a subpopulation of malignant cells, defined by unique properties: a dedifferentiated state, self-renewal, pluripotency, an inherent resistance to chemo- and radiotherapy, the presence of certain epigenetic alterations, as well as a higher tumorigenicity in comparison with the general population of cancer cells. A combination of these features highlights CSCs as a high-priority target during cancer treatment. The presence of CSCs has been confirmed in multiple malignancies, including pancreatic ductal adenocarcinoma, an entity that is well known for its dismal prognosis. As the aggressive course of pancreatic carcinoma is partly attributable to treatment resistance, CSCs could contribute to adverse outcomes. The aim of this review is to summarize the current information regarding the markers and molecular features of CSCs in pancreatic ductal adenocarcinoma and the therapeutic options to remove them.

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Epithelial–mesenchymal plasticity in cancer: signaling pathways and therapeutic targets

Wang,

Xue,

Pang

et al. 2024

MedComm

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Currently, cancer is still a leading cause of human death globally. Tumor deterioration comprises multiple events including metastasis, therapeutic resistance and immune evasion, all of which are tightly related to the phenotypic plasticity especially epithelial–mesenchymal plasticity (EMP). Tumor cells with EMP are manifest in three states as epithelial–mesenchymal transition (EMT), partial EMT, and mesenchymal–epithelial transition, which orchestrate the phenotypic switch and heterogeneity of tumor cells via transcriptional regulation and a series of signaling pathways, including transforming growth factor‐β, Wnt/β‐catenin, and Notch. However, due to the complicated nature of EMP, the diverse process of EMP is still not fully understood. In this review, we systematically conclude the biological background, regulating mechanisms of EMP as well as the role of EMP in therapy response. We also summarize a range of small molecule inhibitors, immune‐related therapeutic approaches, and combination therapies that have been developed to target EMP for the outstanding role of EMP‐driven tumor deterioration. Additionally, we explore the potential technique for EMP‐based tumor mechanistic investigation and therapeutic research, which may burst vigorous prospects. Overall, we elucidate the multifaceted aspects of EMP in tumor progression and suggest a promising direction of cancer treatment based on targeting EMP.

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Inside the stemness engine: Mechanistic links between deregulated transcription factors and stemness in cancer

Cited by 24 publications

References 554 publications

Structural characterization of stem cell factors Oct4, Sox2, Nanog and Esrrb disordered domains, and a method to identify their phospho-dependent binding partners

Structural characterization of stem cell factors Oct4, Sox2, Nanog and Esrrb disordered domains, and a method to identify their phospho-dependent binding partners

Cancer Stem Cells in Pancreatic Ductal Adenocarcinoma

Epithelial–mesenchymal plasticity in cancer: signaling pathways and therapeutic targets

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