Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: April 2, 2024

Cancer stem cells (CSCs) were first discovered in the 1990s, revealing mysteries of cancer origin, migration, recurrence and drug-resistance from a new perspective. The expression pluripotent genes complex signal regulatory networks are significant features CSC, also act as core factors to affect characteristics CSC. Transcription is necessary link regulate phenotype potential involving chromatin environment, nucleosome occupancy, histone modification, transcription factor (TF) availability cis-regulatory elements, which suffer ambient pressure. Especially, activity TFs deeply affected by both internal external factors, foundation CSC transcriptional regulation current research framework. Growing evidence indicates that regulating epigenetic modifications alter stemness effective, some special promoters enhancers can serve targets influence properties Clarifying will assist us directly target key TFs, or hinder through environmental other related order achieve goal inhibiting tumors. This paper comprehensively reviews traditional aspects regulation, explores progress insights impact on status tumor microenvironment (TME), hypoxia, metabolism meaningful conjunction with latest research. Finally, we present opinions omnidirectional targeting CSCs eliminate address resistance.

Language: Английский

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FOXM1 promote the growth and metastasis of uveal melanoma cells by regulating CDK2 expression

International Ophthalmology, Journal Year: 2024, Volume and Issue: 44(1)

Published: Feb. 11, 2024

Abstract Background Uveal melanoma (UVM) is an aggressive malignant tumor originating from melanocytes in the eye. Here, we screened possible genes involved development and prognosis of UVM, identified that FOXM1 MET were associated with UVM patients. Forkhead box protein M1 (FOXM1) a transcription factor regulates expression cell cycle-related are necessary for DNA duplication. However, regulatory mechanism was still not clear. investigated regulation phenotype cells its effect on Methods gene profiles obtained using GSE22138 data omnibus (GEO). Weighted co-expression network analysis (WGCNA) used to construct key module metastasis, which strongly correlated prognosis. The latent biological pathways through ontology analysis. Protein–protein interaction (PPI) networks hub shared authentication performed. GEPIA UALCAN databases relationship between candidate (FOXM1 or MET) abundance examined by quantitative real time polymerase chain reaction (qRT-PCR) western blot. Colony formation counting kit-8 (CCK-8) assays proliferation, wound healing assay migration, transwell invasion Results GEO database showed differentially expressed samples without metastasis constructed WGCNA. PPI revealed seven (VEGFA, KRAS, MET, SRC, EZR, FOXM1, CCNB1) closely metastasis. analyzes suggested related patients UVM. These experimental results highly cells. deficiency represses proliferative, migratory, invasive abilities Conclusions silencing may hinder progression, providing novel theoretical basis new insights treatment.

Language: Английский

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Targeting myeloma metabolism: How abnormal metabolism contributes to multiple myeloma progression and resistance to proteasome inhibitors

Neoplasia, Journal Year: 2024, Volume and Issue: 50, P. 100974 - 100974

Published: Feb. 16, 2024

Multiple myeloma is a hematological malignancy that has evolved from antibody-secreting B lymphocytes. Like other types of cancers, cells have acquired functional capabilities which are referred to as "Hallmarks Cancer", and one their most important features the metabolic disorders. Due high secretory load MM cells, first-line medicine proteasome inhibitors found pronounced effects in for blocking degradation misfolded proteins, leading accumulation ER overwhelming stress. Moreover, been reported be effective by targeting glucose, lipid, amino acid metabolism cells. In this review, we described abnormal three major nutrients, such lipid acids, participate cellular functions. We roles progression, how they could exploited therapeutic purposes, current strategies these metabolites, hoping uncover potential novel targets promote development future approaches.

Language: Английский

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FOXM1: a new therapeutic target of extramammary Paget disease

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 19, 2024

Abstract Extramammary Paget disease (EMPD) is a rare skin cancer that primarily affects older individuals predominantly in areas with apocrine sweat glands. Although most early EMPD lesions are indolent, patients metastatic have poor prognosis due to the lack of effective systemic treatment. In this study, we investigated role forkhead box M1 (FOXM1), potent transcription factor, and assessed potential FOXM1 as therapeutic target. Immunohistochemistry 112 primary 17 samples revealed expression increased tumor progression. Patients whom was expressed more than 10% cells had significantly shorter disease-specific survival other ( p = 0.0397). vitro studies using our newly established cell line, KS-EMPD-1, found high FOXM1. Knockdown impaired viability, migration, invasion. Inhibition thiostrepton also reduced viability dose-dependent manner. These findings suggest promising target for EMPD.

Language: Английский

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Role of vascular endothelial growth factor D in lung adenocarcinoma immunotherapy response

American Journal of Translational Research, Journal Year: 2024, Volume and Issue: 16(6), P. 2263 - 2277

Published: Jan. 1, 2024

To identify key genes associated with tumor-associated macrophages (TAMs), tumor immunotherapy, in the prognosis of lung adenocarcinoma (LUAD).

Language: Английский

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