scholarly journals Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1879
Author(s):  
Zdeněk Kejík ◽  
Robert Kaplánek ◽  
Petr Dytrych ◽  
Michal Masařík ◽  
Kateřina Veselá ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell Lung Carcinoma ◽  
Meta Analysis ◽  
Tumour Cells ◽  
Circulating Tumour Cells ◽  
Cell Lung Carcinoma ◽  
Mesenchymal Transition ◽  
Standard Methods ◽  
The Impact

Designing optimal (neo)adjuvant therapy is a crucial aspect of the treatment of non-small-cell lung carcinoma (NSCLC). Standard methods of chemotherapy, radiotherapy, and immunotherapy represent effective strategies for treatment. However, in some cases with high metastatic activity and high levels of circulating tumour cells (CTCs), the efficacy of standard treatment methods is insufficient and results in treatment failure and reduced patient survival. CTCs are seen not only as an isolated phenomenon but also a key inherent part of the formation of metastasis and a key factor in cancer death. This review discusses the impact of NSCLC therapy strategies based on a meta-analysis of clinical studies. In addition, possible therapeutic strategies for repression when standard methods fail, such as the administration of low-toxicity natural anticancer agents targeting these phenomena (curcumin and flavonoids), are also discussed. These strategies are presented in the context of key mechanisms of tumour biology with a strong influence on CTC spread and metastasis (mechanisms related to tumour-associated and -infiltrating cells, epithelial–mesenchymal transition, and migration of cancer cells).

scholarly journals Spectrum of Epithelial-Mesenchymal Transition Phenotypes in Circulating Tumour Cells from Early Breast Cancer Patients

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 59 ◽  
Author(s):  
Aleksandra Markiewicz ◽  
Justyna Topa ◽  
Anna Nagel ◽  
Jaroslaw Skokowski ◽  
Barbara Seroczynska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Tumour Cells ◽  
Molecular Heterogeneity ◽  
Stem Cell Markers ◽  
Circulating Tumour Cells ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition

Circulating tumour cells (CTCs) can provide valuable prognostic information in a number of epithelial cancers. However, their detection is hampered due to their molecular heterogeneity, which can be induced by the epithelial-mesenchymal transition (EMT) process. Therefore, current knowledge about CTCs from clinical samples is often limited due to an inability to isolate wide spectrum of CTCs phenotypes. In the current work, we aimed at isolation and molecular characterization of CTCs with different EMT status in order to establish their clinical significance in early breast cancer patients. We have obtained CTCs-enriched blood fraction from 83 breast cancer patients in which we have tested the expression of epithelial, mesenchymal and general breast cancer CTCs markers (MGB1/HER2/CK19/CDH1/CDH2/VIM/PLS3), cancer stem cell markers (CD44, NANOG, ALDH1, OCT-4, CD133) and cluster formation gene (plakoglobin). We have shown that in the CTCs-positive patients, epithelial, epithelial-mesenchymal and mesenchymal CTCs markers were detected at a similar rate (in 28%, 24% and 24%, respectively). Mesenchymal CTCs were characterized by the most aggressive phenotype (significantly higher expression of CXCR4, uPAR, CD44, NANOG, p < 0.05 for all), presence of lymph node metastases (p = 0.043), larger tumour size (p = 0.023) and 7.33 higher risk of death in the multivariate analysis (95% CI 1.06–50.41, p = 0.04). Epithelial-mesenchymal subtype, believed to correspond to highly plastic and aggressive state, did not show significant impact on survival. Gene expression profile of samples with epithelial-mesenchymal CTCs group resembled pure epithelial or pure mesenchymal phenotypes, possibly underlining degree of EMT activation in particular patient’s sample. Molecular profiling of CTCs EMT phenotype provides more detailed and clinically informative results, proving the role of EMT in malignant cancer progression in early breast cancer.

scholarly journals The crosstalk between p38 and Akt signaling pathways orchestrates EMT by regulating SATB2 expression in NSCLC cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (9) ◽  
pp. 101042831770621 ◽  
Author(s):  
Hakan Kucuksayan ◽  
Hakan Akca
Keyword(s):  
Lung Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Binding Protein ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Carcinoma Cells ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Mesenchymal Transition ◽  
Lung Carcinoma Cells

Epithelial–mesenchymal transition is a crucial event for metastasis and could be mediated by several pathways such as phosphoinositide 3-kinase/Akt, mitogen-activated protein kinases, as well as many epigenetic regulators. Special AT-rich sequence-binding protein 2 is an epigenetic regulator involved in epithelial–mesenchymal transition and osteoblastic differentiation. It has been reported that the crosstalk between several pathways is responsible for the regulation of epithelial–mesenchymal transition in cancer cells. However, crosstalks between p38 and Akt pathways involved in epithelial–mesenchymal transition are still unknown. We recently reported that there is a crosstalk between p38 and Akt pathways in non-small-cell lung carcinoma cells, and this crosstalk is associated with E-cadherin and special AT-rich sequence-binding protein 2 expressions. Therefore, we aimed to determine whether this crosstalk has a mediator role in the regulation of epithelial–mesenchymal transition in non-small-cell lung carcinoma. Our results showed that inhibition of p38 leads to the disruption of this crosstalk via decreased expression of phosphatase and tensin homolog (PTEN) and subsequently increased activation of Akt in non-small-cell lung carcinoma cells. Then, we found that p38 inhibition upregulated special AT-rich sequence-binding protein 2 expression and reversed epithelial–mesenchymal transition in non-small-cell lung carcinoma cells. Furthermore, special AT-rich sequence-binding protein 2 knockdown abolished the effect of p38 inhibition on epithelial–mesenchymal transition in non-small-cell lung carcinoma cells. In conclusion, our results strongly indicate that the crosstalk between p38 and Akt pathways can determine special AT-rich sequence-binding protein 2 expression and epithelial character of non-small-cell lung carcinoma cells, and special AT-rich sequence-binding protein 2 is a critical epigenetic regulator for epithelial–mesenchymal transition mediated by p38 pathway in non-small-cell lung carcinoma. Our findings will contribute to illuminate the molecular mechanisms of the epithelial–mesenchymal transition process that has a critical significance for lung cancer metastasis.

Sign in / Sign up

Export Citation Format

Share Document