The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity

Frontiers in Oncology, Journal Year: 2018, Volume and Issue: 8

Published: Oct. 9, 2018

The microenvironment encompasses all components of a tumor other than the cancer cells themselves. It is highly heterogenous, comprising cellular component that includes immune cells, fibroblasts, adipocytes and endothelial non-cellular component, which meshwork polymeric proteins accessory molecules, termed extra-cellular matrix (ECM). ECM provides both biochemical biomechanical context within exist. Cancer progression dependent on ability to traverse barrier, access circulation establish distal metastases. Communication between therefore an important aspect progression. Significant progress has been made in identifying molecular mechanisms enable subvert facilitate growth spread. While much less known about how adapt changes nor indeed they influence structure composition, importance now well established. Plasticity refers modify their physiological characteristics, permitting them survive hostile microenvironments resist therapy. Examples include acquisition stemness characteristics epithelial-mesenchymal mesenchymal-epithelial transitions. There emerging evidence properties cell plasticity vice versa. Outstanding challenges for field remain identification by tumor-promoting delineating key underlying ECM-induced plasticity. Here we summarize current state understanding relationships main stromal types determine pathways govern this three-way interaction regulate We postulate comprehensive dynamic system will be required fully exploit opportunities targeting regulators

Language: Английский

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Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities

Genes & Development, Journal Year: 2019, Volume and Issue: 33(19-20), P. 1295 - 1318

Published: Oct. 1, 2019

An incomplete view of the mechanisms that drive metastasis, primary cause cancer-related death, has been a major barrier to development effective therapeutics and prognostic diagnostics. Increasing evidence indicates interplay between microenvironment, genetic lesions, cellular plasticity drives metastatic cascade resistance therapies. Here, using melanoma as model, we outline diversity trajectories cell states during dissemination therapy exposure, highlight how understanding magnitude dynamics nongenetic reprogramming in space time at single-cell resolution can be exploited develop therapeutic strategies capitalize on tumor evolution.

Language: Английский

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Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies

Cells, Journal Year: 2019, Volume and Issue: 8(8), P. 840 - 840

Published: Aug. 5, 2019

Recent biomedical discoveries have revolutionized the concept and understanding of carcinogenesis, a complex multistep phenomenon which involves accretion genetic, epigenetic, biochemical, histological changes, with special reference to MicroRNAs (miRNAs) cancer stem cells (CSCs). miRNAs are small noncoding molecules known regulate expression more than 60% human genes, their aberrant has been associated pathogenesis cancers regulation stemness features CSCs. CSCs population present in malignancies well-known for resistance, relapse, tumorigenesis, poor clinical outcome compels development novel effective therapeutic protocols better outcome. Interestingly, role maintaining regulating functioning through targeting various oncogenic signaling pathways, such as Notch, wingless (WNT)/β-Catenin, janus kinases/ signal transducer activator transcription (JAK/STAT), phosphatidylinositol 3-kinase/ protein kinase B (PI3/AKT), nuclear factor kappa-light-chain-enhancer activated (NF-kB), is critical poses huge challenge treatment. Based on recent findings, here, we documented regulatory action or underlying mechanisms how affect pathways attributed CSCs, self-renewal, differentiation, epithelial mesenchymal transition (EMT), metastasis, resistance recurrence etc., types including colorectal cancer, lung breast head neck prostate liver etc. We also shed light fact that targeted attenuation deregulated miRNA related carcinogenesis could be viable approach

Language: Английский

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Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer

Cell stem cell, Journal Year: 2020, Volume and Issue: 26(4), P. 569 - 578.e7

Published: March 12, 2020

Colorectal cancer stem cells (CSCs) express Lgr5 and display extensive cell-like multipotency self-renewal are thought to seed metastatic disease. Here, we used a mouse model of colorectal (CRC) human tumor xenografts investigate the cell origin metastases. We found that most disseminated CRC in circulation were Lgr5− formed distant metastases which Lgr5+ CSCs appeared. This plasticity occurred independently stemness-inducing microenvironmental factors was indispensable for outgrowth, but not establishment, Together, these findings show seeded by cells, intrinsic capacity become niche-independent manner can restore epithelial hierarchies tumors.

Language: Английский

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lncRNA involvement in cancer stem cell function and epithelial-mesenchymal transitions

Seminars in Cancer Biology, Journal Year: 2020, Volume and Issue: 75, P. 38 - 48

Published: Dec. 18, 2020

Language: Английский

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STAT3, stem cells, cancer stem cells and p63

Cellular & Molecular Biology Letters, Journal Year: 2018, Volume and Issue: 23(1)

Published: March 22, 2018

Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor with many important functions in the biology normal transformed cells. Its regulation highly complex as it involved signaling pathways different cell types under wide variety conditions. Besides other functions, STAT3 an regulator stem cells cancer p63 which member p53 protein family also these both physically functionally connected STAT3. This review summarizes function regulation, its role properties highlights recent reports about relationship to p63.

Language: Английский

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Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action

Medicinal Research Reviews, Journal Year: 2017, Volume and Issue: 37(6), P. 1492 - 1517

Published: June 23, 2017

Abstract Artemisinin and its derivatives (collectively termed as artemisinins) are among the most important effective antimalarial drugs, with proven safety efficacy in clinical use. Beyond their effects, artemisinins have also been shown to possess selective anticancer properties, demonstrating cytotoxic effects against a wide range of cancer types both vitro vivo. These appear be mediated by artemisinin‐induced changes multiple signaling pathways, interfering simultaneously hallmarks cancer. Great strides taken characterize these pathways reveal mechanisms action artemisinin. Moreover, encouraging data obtained from limited number trials support property. However, there several key gaps knowledge that continue serve significant barriers repurposing agents. This review focuses on emerging aspects this field, highlighting breakthroughs unresolved questions well novel techniques approaches recent studies. We discuss mechanism artemisinin activation cancer, findings regards target proteins new understandings cell death mechanisms, practical issues believe will topics realizing potential safe potent

Language: Английский

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Triggered ferroptotic polymer micelles for reversing multidrug resistance to chemotherapy

Biomaterials, Journal Year: 2019, Volume and Issue: 223, P. 119486 - 119486

Published: Sept. 7, 2019

Language: Английский

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Tumor-initiating cells establish an IL-33–TGF-β niche signaling loop to promote cancer progression

Science, Journal Year: 2020, Volume and Issue: 369(6501)

Published: July 17, 2020

Targeting the cross-talk between tumor-initiating cells (TICs) and niche microenvironment is an attractive avenue for cancer therapy. We show here, using a mouse model of squamous cell carcinoma, that TICs play crucial role in creating required tumor progression drug resistance. Antioxidant activity TICs, mediated by transcription factor NRF2, facilitates release nuclear cytokine, interleukin-33 (IL-33). This cytokine promotes differentiation macrophages express high-affinity immunoglobulin E receptor FcεRIα are close proximity to TICs. In turn, these IL-33-responding

Language: Английский

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CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer

Cells, Journal Year: 2020, Volume and Issue: 9(7), P. 1651 - 1651

Published: July 9, 2020

Radiotherapy (RT) is a modality of oncologic treatment that can be used to treat approximately 50% all cancer patients either alone or in combination with other modalities such as surgery, chemotherapy, immunotherapy, and therapeutic targeting. Despite the technological advances RT, which allow more precise delivery radiation while progressively minimizing impact on normal tissues, issues like radioresistance tumor recurrence remain important challenges. Tumor heterogeneity responsible for variation response different subpopulations. A main factor related presence stem cells (CSC) inside tumors, are metastases, relapses, RT failure, poor prognosis patients. The plasticity CSCs, process highly dependent epithelial–mesenchymal transition (EMT) associated cell dedifferentiation, complicates identification eradication CSCs it might involved disease relapse progression after irradiation. microenvironment interactions their niches also play an role RT. This review provides deep insight into characteristics mechanisms both primary metastasis radiation, radiobiological principles CSC Finally, we summarize major clinical trials development CSC-based therapies combined overcome radioresistance. better understanding potential targets radiosensitization will provide safer efficient strategies, turn improve live expectancy curability

Language: Английский

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