CKAP2L, transcriptionally inhibited by FOXP3, promotes breast carcinogenesis through the AKT/mTOR pathway

Chi, Feng; Chen, Long; Jin, Xiaoming; He, Gang; Liu, Zhen; Han, Sijia

doi:10.1016/j.yexcr.2022.113035

Cited by 11 publications

(8 citation statements)

References 48 publications

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“…Xiong et al discovered that upregulation of CKAP2L in lung adenocarcinoma (LAD) promoted cell proliferation partially by regulating the MAPK signaling pathway, which was also predictive of poor prognosis of LAD patients [9]. Related research reports that CKAP2L could activate the AKT/mTOR signaling pathway in cancer cells and promotes carcinogenesis [22]. Meanwhile, CKAP2L is a vital regulator of miR-4496 activity, and facilitates glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition [21].…”

Section: Discussionmentioning

confidence: 99%

CKAP2L Promotes Esophageal Squamous Cell Carcinoma Progression and Drug-Resistance by Modulating Cell Cycle

Chen

Wang

et al. 2022

Journal of Oncology

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Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer and the leading cause of cancer-related mortality worldwide, especially in Asia. In this study, the gene CKAP2L was selected by GEO, TCGA, and GTEx database analysis. The high expression of CKAP2L is related to the occurrence and development of ESCC. In addition, CKAP2L knockdown can inhibit the growth and migration of ESCC cells, while CKAP2L overexpression has the opposite effect. Furthermore, in vivo experiments indicated that down-regulation of CKAP2L can inhibit the tumorigenesis of ESCC cells. KEGG pathway analysis and the STRING database explored the relationship between cell cycle and CKAP2L and verified that depletion of CKAP2L markedly arrested cell cycle in the G2/M phase. Meanwhile, CKAP2L knockdown increased the sensitivity of ESCC cells to flavopiridol, the first CDK inhibitor to be tested in clinical trials, leading to an observable reduction in cell proliferation and an increase in cellular apoptosis. In brief, we identified CKAP2L as a tumor promoter, potential prognostic indicator, and therapeutic target of ESCC, which may play a role in regulating cell cycle progression.

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Section: Discussionmentioning

confidence: 99%

CKAP2L Promotes Esophageal Squamous Cell Carcinoma Progression and Drug-Resistance by Modulating Cell Cycle

Chen

Wang

et al. 2022

Journal of Oncology

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“…These effects on cell cycle and cell division were further confirmed by IPA, which predicted inhibition of cell cycle control of chromosomal replication, organization of cytoskeleton, repair of DNA, transcription, and segregation of chromosomes ( Table S5 ; Table S6 ). Besides this, several positive regulators of cell cycle progression, such as CKAP2L ( 41 ), E2F1 ( 42 ), and EP400 ( 43 ), were predicted as inhibited upstream regulators ( Table S7 ), whereas activation was predicted for the retinoblastoma (Rb) protein, which plays a pivotal role in negative regulation of the cell cycle ( 44 ).…”

Section: Resultsmentioning

confidence: 99%

Glucocorticoid receptor hypersensitivity enhances inflammatory signaling and inhibits cell cycle progression in porcine PBMCs

Hadlich²,

Wimmers³

et al. 2022

Front. Immunol.

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The consequences of glucocorticoid receptor (GR) hypersensitivity during infection have so far received little attention. We previously discovered that a natural gain-of-function Ala610Val substitution in the porcine GR aggravates response of pigs to lipopolysaccharide (LPS)-induced endotoxemia, which can be alleviated by dexamethasone (DEX) pretreatment. In this work, we investigated the relevant molecular basis of these phenotypes by transcriptomic profiling of porcine peripheral blood mononuclear cells (PBMCs) carrying different GR genotypes, in unstimulated conditions or in response to DEX and/or LPS in vitro. The Val allele differentially regulated abunda+nt genes in an additive-genetic manner. A subset of more than 200 genes was consistently affected by the substitution across treatments. This was associated with upregulation of genes related i.a. to endo-lysosomal system, lipid and protein catabolism, and immune terms including platelet activation, and antigen presentation, while downregulated genes were mainly involved in cell cycle regulation. Most importantly, the set of genes constitutively upregulated by Val includes members of the TLR4/LPS signaling pathway, such as LY96. Consequently, when exposing PBMCs to LPS treatment, the Val variant upregulated a panel of additional genes related to TLR4 and several other pattern recognition receptors, as well as cell death and lymphocyte signaling, ultimately amplifying the inflammatory responses. In contrast, when stimulated by DEX treatment, the Val allele orchestrated several genes involved in anti-inflammatory responses during infection. This study provides novel insights into the impact of GR hypersensitivity on the fate and function of immune cells, which may be useful for endotoxemia therapy.

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“…When looking at the co-expression relationship of the host gene and individual viral gene, we only found host gene CKAP2L was positively correlated with E7. CKAP2L was found to be highly expressed in hepatocellular cancer, lung adenocarcinoma, and breast cancer, [67][68][69] where CKAP2L was proposed as a potential target gene for tumor therapy. We hypothesized that CKAP2L might also participate in the development of cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of HPV oncogene and host cell differentiation associated cellular heterogeneity in cervical cancer via single‐cell transcriptomic analysis

Li,

Wang,

et al. 2023

Journal of Medical Virology

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Human Papillomaviruses (HPVs) are associated with around 5%–10% of human cancer, notably nearly 99% of cervical cancer. The mechanisms HPV interacts with stratified epithelium (differentiated layers) during the viral life cycle, and oncogenesis remain unclear. In this study, we used single‐cell transcriptome analysis to study viral gene and host cell differentiation‐associated heterogeneity of HPV‐positive cervical cancer tissue. We examined the HPV16 genes—E1, E6, and E7, and found they expressed differently across nine epithelial clusters. We found that three epithelial clusters had the highest proportion of HPV‐positive cells (33.6%, 37.5%, and 32.4%, respectively), while two exhibited the lowest proportions (7.21% and 5.63%, respectively). Notably, the cluster with the most HPV‐positive cells deviated significantly from normal epithelial layer markers, exhibiting functional heterogeneity and altered epithelial structuring, indicating that significant molecular heterogeneity existed in cancer tissues and that these cells exhibited unique/different gene signatures compared with normal epithelial cells. These HPV‐positive cells, compared to HPV‐negative, showed different gene expressions related to the extracellular matrix, cell adhesion, proliferation, and apoptosis. Further, the viral oncogenes E6 and E7 appeared to modify epithelial function via distinct pathways, thus contributing to cervical cancer progression. We investigated the HPV and host transcripts from a novel viewpoint focusing on layer heterogeneity. Our results indicated varied HPV expression across epithelial clusters and epithelial heterogeneity associated with viral oncogenes, contributing biological insights to this critical field of study.

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CKAP2L, transcriptionally inhibited by FOXP3, promotes breast carcinogenesis through the AKT/mTOR pathway

Cited by 11 publications

References 48 publications

CKAP2L Promotes Esophageal Squamous Cell Carcinoma Progression and Drug-Resistance by Modulating Cell Cycle

CKAP2L Promotes Esophageal Squamous Cell Carcinoma Progression and Drug-Resistance by Modulating Cell Cycle

Glucocorticoid receptor hypersensitivity enhances inflammatory signaling and inhibits cell cycle progression in porcine PBMCs

Identification of HPV oncogene and host cell differentiation associated cellular heterogeneity in cervical cancer via single‐cell transcriptomic analysis

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