Oxaliplatin and irinotecan induce heterogenous changes in the EMT markers of metastasizing colorectal carcinoma cells

Skarkova, Veronika; Králová, Věra; Krbal, Lukáš; Matoušková, Petra; Soukup, Jiří; Rudolf, Emil

doi:10.1016/j.yexcr.2018.05.032

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…Studies have revealed numerous mechanisms underlying chemoresistance, such as the reduction in cellular accumulation, intracellular inactivation, blocking of apoptosis induction, and enhancement of DNA repair [ 29 , 30 ]. Recent findings indicate that EMT may have a key role in mediating chemotherapy resistance in tumor cells [ 6 , 8 ]. In addition, overexpression of transcription factors of EMT, such as Twist, Slug, Snail, and ZEB, in drug-resistant cells has been related to enhanced metastatic ability and resistance to apoptosis, whereas downregulation of these transcription factors rendered cells susceptible to chemotherapy-induced apoptosis [ 7 , 10 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

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Reelin Promotes Cisplatin Resistance by Induction of Epithelial-Mesenchymal Transition via p38/GSK3β/Snail Signaling in Non-Small Cell Lung Cancer

Fang

et al. 2020

Med Sci Monit

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Background Emerging evidence suggests the involvement of Reelin in chemoresistance in various cancers. However, its function in cisplatin (DDP) sensitivity of non-small cell lung cancer (NSCLC) needs to be investigated. Material/Methods Reelin expression in cisplatin-sensitive A549 cells and cisplatin-resistant NSCLC (A549/DDP) cells was analyzed by western blot analysis. qRT-PCR, western blotting, immunofluorescence, CCK-8 assays, Annexin V/propidium iodide apoptosis assay, and Transwell migration assays were carried out to determine the function of Reelin on DDP resistance. Results Reelin was markedly increased in A549/DDP cells relative to A549 cells. Knockdown of Reelin enhanced DDP chemosensitivity of A549/DDP cells, whereas overexpression of Reelin enhanced DDP resistance of A549, H1299, and H460 cells. Reelin induced DDP resistance in NSCLC cells via facilitating epithelial-mesenchymal transition (EMT). Furthermore, Reelin modulated p38/GSK3β signal transduction and promoted Snail (EMT-associated transcription factor) expression. Suppression of p38/Snail reversed Reelin-induced EMT and resistance of NSCLC cells to DDP. Conclusions These data indicated that Reelin induces DDP resistance of NSCLC by regulation of the p38/GSK3β/Snail/EMT signaling pathway and provide evidence that Reelin suppression can be an effective strategy to suppress DDP resistance in NSCLC.

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Section: Discussionmentioning

confidence: 99%

“…Epithelial-mesenchymal transition (EMT) is a vital step in embryonic development, wound healing, tumor invasion, tissue remodeling, and metastasis [ 5 , 6 ]. EMT is associated with increased expressions of the mesenchymal markers vimentin and N-cadherin and decreased levels of the epithelial marker E-cadherin.…”

Section: Introductionmentioning

confidence: 99%

Reelin Promotes Cisplatin Resistance by Induction of Epithelial-Mesenchymal Transition via p38/GSK3β/Snail Signaling in Non-Small Cell Lung Cancer

Fang

et al. 2020

Med Sci Monit

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“…Both forward and reverse primers were, in final concentrations, 100 nM. The PCR reactions were performed as described in [23].…”

Section: Methodsmentioning

confidence: 99%

The Evaluation of Glioblastoma Cell Dissociation and Its Influence on Its Behavior

Skarkova

Krupova

Vitovcova

et al. 2019

IJMS

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Purpose: Primary cell lines are a valuable tool for evaluation of tumor behavior or sensitivity to anticancer treatment and appropriate dissociation of cells could preserve genomic profile of the original tissue. The main aim of our study was to compare the influence of two methods of glioblastoma multiforme (GBM) cell derivation (mechanic—MD; enzymatic—ED) on basic biological properties of thus derived cells and correlate them to the ones obtained from stabilized GBM cell line A-172. Methods: Cell proliferation and migration (xCELLigence Real-Time Cell Analysis), expression of microRNAs and protein markers (RT-PCR and Western blotting), morphology (phase contrast and fluorescent microscopy), and accumulation of temozolomide (TMZ) and its metabolite 5-aminoimidazole-4-carboxamide (AIC) inside the cells (LC-MS analysis) were carried out in five different samples of GBM (GBM1, GBM2, GBM32, GBM33, GBM34), with each of them processed by MD and ED types of isolations. The same analyses were done in the A-172 cell line too. Results: Primary GBM cells obtained by ED or MD approaches significantly differ in biological behavior and properties of these cells. Unlike in primary MD GBM cells, higher proliferation, as well as migration, was observed in primary ED GBM cells, which were also associated with the acquired mesenchymal phenotype and higher sensitivity to TMZ. Finally, the same analyses of stabilized GBM cell line A-172 revealed several important differences in measured parameters. Conclusions: GBM cells obtained by MD and ED dissociation show considerable heterogeneity, but based on our results, MD approach should be the preferred method of primary GBM cell isolation

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“…Yang et al showed in vitro that a TWIST1-induced CSC-like phenotype contributes to develop resistance to irinotecan and enhances migration and invasiveness of colon cancer cells [ 229 ]. Skarkova et al [ 230 ] first addressed the expression of EMT markers in CRC cell lines obtained from primary tumors and paired lymph node metastases of three patients. They showed the variation of EMT markers after irinotecan and oxaliplatin treatments, by using qRT-PCR, Western blot, migration assay, and cytotoxicity tests.…”

Section: Emt and Chemoresistance: An Open Issuementioning

confidence: 99%

Epithelial to Mesenchymal Transition: A Challenging Playground for Translational Research. Current Models and Focus on TWIST1 Relevance and Gastrointestinal Cancers

Greco

Rubbino

Morelli

et al. 2021

IJMS

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Resembling the development of cancer by multistep carcinogenesis, the evolution towards metastasis involves several passages, from local invasion and intravasation, encompassing surviving anoikis into the circulation, landing at distant sites and therein establishing colonization, possibly followed by the outgrowth of macroscopic lesions. Within this cascade, epithelial to mesenchymal transition (EMT) works as a pleiotropic program enabling cancer cells to overcome local, systemic, and distant barriers against diffusion by replacing traits and functions of the epithelial signature with mesenchymal-like ones. Along the transition, a full-blown mesenchymal phenotype may not be accomplished. Rather, the plasticity of the program and its dependency on heterotopic signals implies a pendulum with oscillations towards its reversal, that is mesenchymal to epithelial transition. Cells in intermixed EÛM states can also display stemness, enabling their replication together with the epithelial reversion next to successful distant colonization. If we aim to include the EMT among the hallmarks of cancer that could modify clinical practice, the gap between the results pursued in basic research by animal models and those achieved in translational research by surrogate biomarkers needs to be filled. We review the knowledge on EMT, derived from models and mechanistic studies as well as from translational studies, with an emphasis on gastrointestinal cancers (GI).

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Oxaliplatin and irinotecan induce heterogenous changes in the EMT markers of metastasizing colorectal carcinoma cells

Cited by 9 publications

References 34 publications

Reelin Promotes Cisplatin Resistance by Induction of Epithelial-Mesenchymal Transition via p38/GSK3β/Snail Signaling in Non-Small Cell Lung Cancer

Reelin Promotes Cisplatin Resistance by Induction of Epithelial-Mesenchymal Transition via p38/GSK3β/Snail Signaling in Non-Small Cell Lung Cancer

The Evaluation of Glioblastoma Cell Dissociation and Its Influence on Its Behavior

Epithelial to Mesenchymal Transition: A Challenging Playground for Translational Research. Current Models and Focus on TWIST1 Relevance and Gastrointestinal Cancers

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