Cell stemness, epithelial-to-mesenchymal transition, and immunoevasion: Intertwined aspects in cancer metastasis

Romano, Simona; Tufano, Martina; D’Arrigo, Paolo; Vigorito, Vincenza; Russo, Salvatore; Romano, Maria

doi:10.1016/j.semcancer.2019.08.015

Cited by 33 publications

(20 citation statements)

References 115 publications

(175 reference statements)

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“…Muhammad et al revealed that c-Fos overexpression promotes EMT, cell stemness, and tumor growth when compared with control cells [ 28 ]. Cancer cells with increased stemness have stronger self-renewal and tumorigenesis abilities and contribute to adverse clinical outcomes [ 29 ]. Previous studies illustrated that FOXD1 can regulate the stemness of mesenchymal glioma stem cells [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2

et al. 2021

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Background Epithelial-mesenchymal transition (EMT) and cell stemness are implicated in the initiation and progression of oral squamous cell carcinoma (OSCC). Revealing the intrinsic regulatory mechanism may provide effective therapeutic targets for OSCC. Results In this study, we found that Forkhead box D1 (FOXD1) was upregulated in OSCC compared with normal samples. Patients with a higher FOXD1 expression had a poorer overall survival and disease-free survival. Immunohistochemical staining results showed that FOXD1 expression was related to the clinical stage and relapse status of OSCC patients. When FOXD1 expression was knocked down in CAL27 and SCC25 cells, the migration, invasion, colony formation, sphere formation, and proliferation abilities decreased. Moreover, EMT and stemness-related markers changed remarkably, which indicated that the EMT process and cell stemness were inhibited. Conversely, overexpression of FOXD1 promoted EMT and cell stemness. Further study demonstrated that FOXD1 could bind to the promoter region and activate the transcription of SNAI2. In turn, the elevated SNAI2 affected EMT and cell stemness. An in vivo study showed that FOXD1-overexpressing CAL27 cells possessed a stronger tumorigenic ability. Conclusions Our findings revealed a novel mechanism in regulating EMT and cell stemness and proposed FOXD1 as a potential marker for the diagnosis and treatment of OSCC.

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Section: Discussionmentioning

confidence: 99%

FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2

et al. 2021

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“…6f), it was suggested that drug resistance was related to immune response in glioma patients. It has also been reported that immune response and immune genes like B7H3 and Tim3 can contribute to the stemness and drug resistance [21,22]. Then, the relationship between risk signature and immune checkpoints, including B7H3, B7H4, Tim3, PD1, and PDL1 were analyzed [23,24].…”

Section: Potential Mechanisms Of Drug Resistance In Gliomamentioning

confidence: 99%

Comprehensive profiling identifies a novel signature with robust predictive value and reveals the potential drug resistance mechanism in glioma

et al. 2020

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Background: Gliomas are the most common and malignant brain tumors. The standard therapy is surgery combined with radiotherapy, chemotherapy, and/or other comprehensive methods. However, the emergence of chemoresistance is the main obstacle in treatment and its mechanism is still unclear. Methods: We firstly developed a multi-gene signature by integrated analysis of cancer stem cell and drug resistance related genes. The Chinese Glioma Genome Atlas (CGGA, 325 samples) and The Cancer Genome Atlas (TCGA, 699 samples) datasets were then employed to verify the efficacy of the risk signature and investigate its significance in glioma prognosis. GraphPad Prism, SPSS and R language were used for statistical analysis and graphical work. Results: This signature could distinguish the prognosis of patients, and patients with high risk score exhibited short survival time. The Cox regression and Nomogram model indicated the independent prognostic performance and high prognostic accuracy of the signature for survival. Combined with a well-known chemotherapy impact factor-MGMT promoter methylation status, this risk signature could further subdivide patients with distinct survival. Functional analysis of associated genes revealed signature-related biological process of cell proliferation, immune response and cell stemness. These mechanisms were confirmed in patient samples. Conclusions: The signature was an independent and powerful prognostic biomarker in glioma, which would improve risk stratification and provide a more accurate assessment of personalized treatment.

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“…PD-L1, also known as CD274 or B7-H1, is a transmembrane protein physiologically expressed on the plasma membrane of antigen presenting cells and aberrantly expressed by tumor cells, supporting tumor immune evasion [ 1 ]. Tumor PD-L1 expression can be constitutive or acquired [ 2 ]. Genetic/epigenetic alterations, deregulated activation of oncogenic signaling pathways and stimuli from microenvironment [ 2 ] are among the causes of aberrant expression of such an immune modulatory ligand in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

PD-L1 Expression Fluctuates Concurrently with Cyclin D in Glioblastoma Cells

Tufano

D’Arrigo

D’Agostino

et al. 2021

Cells

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Despite Glioblastoma (GBM) frequently expressing programmed cell death ligand-1 (PD-L1), treatment with anti-programmed cell death-1 (PD1) has not yielded brilliant results. Intratumor variability of PD-L1 can impact determination accuracy. A previous study on mouse embryonic fibroblasts (MEFs) reported a role for cyclin-D in control of PD-L1 expression. Because tumor-cell growth within a cancer is highly heterogeneous, we looked at whether PD-L1 and its cochaperone FKBP51s were influenced by cell proliferation, using U251 and SF767 GBM-cell-lines. PD-L1 was measured by Western blot, flow cytometry, confocal-microscopy, quantitative PCR (qPCR), CCND1 by qPCR, FKBP51s by Western blot and confocal-microscopy. Chromatin-Immunoprecipitation assay (xChIp) served to assess the DNA-binding of FKBP51 isoforms. In the course of cell culture, PD-L1 appeared to increase concomitantly to cyclin-D on G1/S transition, to decrease during exponential cell growth progressively. We calculated a correlation between CCND1 and PD-L1 gene expression levels. In the temporal window of PD-L1 and CCND1 peak, FKBP51s localized in ER. When cyclin-D declined, FKBP51s went nuclear. XChIp showed that FKBP51s binds CCND1 gene in a closed-chromatin configuration. Our finding suggests that the dynamism of PD-L1 expression in GBM follows cyclin-D fluctuation and raises the hypothesis that FKBP51s might participate in the events that govern cyclin-D oscillation.

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Cell stemness, epithelial-to-mesenchymal transition, and immunoevasion: Intertwined aspects in cancer metastasis

Cited by 33 publications

References 115 publications

FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2

FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2

Comprehensive profiling identifies a novel signature with robust predictive value and reveals the potential drug resistance mechanism in glioma

PD-L1 Expression Fluctuates Concurrently with Cyclin D in Glioblastoma Cells

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