The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity DOI Creative Commons
Valentina Poltavets, Marina Kochetkova, Stuart M. Pitson

et al.

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

The metabolism of cancer cells during metastasis DOI
Gabriele Bergers, Sarah‐Maria Fendt

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(3), P. 162 - 180

Published: Jan. 18, 2021

Language: Английский

Citations

669
Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis DOI Creative Commons
Mohit Kumar Jolly, Marcelo Boareto, Bin Huang

et al.

Frontiers in Oncology, Journal Year: 2015, Volume and Issue: 5

Published: Jan. 1, 2015

Understanding cell-fate decisions during tumorigenesis and metastasis is a major challenge in modern cancer biology. One canonical decision that cells undergo Epithelial-to-Mesenchymal Transition (EMT) its reverse Mesenchymal-to-Epithelial (MET). While transitioning between these two phenotypes – epithelial mesenchymal, can also attain hybrid epithelial/ mesenchymal (i.e. partial or intermediate EMT) phenotype. Cells this phenotype have mixed (eg. adhesion) migration) properties, thereby allowing them to move collectively as clusters of Circulating Tumor (CTCs). If enter the circulation, they be more apoptosis-resistant capable initiating metastatic lesions than moving individually with wholly phenotypes, having undergone complete EMT. Here, we review operating principles core regulatory network for EMT/MET acts ‘three-way’ switch giving rise three distinct epithelial, epithelial/mesenchymal. We further characterize E/M terms capabilities collective cell migration, tumor-initiation, cell-cell communication, drug resistance. elucidate how highly interconnected coupling modules coordinates among population dynamic tumor, hence facilitating tumor-stroma interactions, formation CTC clusters, consequently metastasis. Finally, discuss multiple advantages epithelial/mesenchymal compared EMT argue migrating are primary ‘bad actors’

Language: Английский

Citations

643
Visualization and targeting of LGR5+ human colon cancer stem cells DOI

Mariko Shimokawa,

Yuki Ohta, Shingo Nishikori

et al.

Nature, Journal Year: 2017, Volume and Issue: 545(7653), P. 187 - 192

Published: March 27, 2017

Language: Английский

Citations

632
Targeting signalling pathways and the immune microenvironment of cancer stem cells — a clinical update DOI
Joseph Clara, Cecilia Monge, Yingzi Yang

et al.

Nature Reviews Clinical Oncology, Journal Year: 2019, Volume and Issue: 17(4), P. 204 - 232

Published: Dec. 2, 2019

Language: Английский

Citations

620
Concise Review: Emerging Role of CD44 in Cancer Stem Cells: A Promising Biomarker and Therapeutic Target DOI Creative Commons
Yongmin Yan, Xiangsheng Zuo, Daoyan Wei

et al.

Stem Cells Translational Medicine, Journal Year: 2015, Volume and Issue: 4(9), P. 1033 - 1043

Published: July 1, 2015

Abstract The reception and integration of the plethora signals a cell receives from its microenvironment determines cell's fate. CD44 functions as receptor for hyaluronan many other extracellular matrix components, well cofactor growth factors cytokines, thus, is signaling platform that integrates cellular microenvironmental cues with factor cytokine transduces to membrane-associated cytoskeletal proteins or nucleus regulate variety gene expression levels related cell-matrix adhesion, migration, proliferation, differentiation, survival. Accumulating evidence indicates CD44, especially CD44v isoforms, are cancer stem (CSC) markers critical players in regulating properties CSCs, including self-renewal, tumor initiation, metastasis, chemoradioresistance. Furthermore, there ample valuable prognostic various types tumors. Therefore, therapies target may destroy CSC population, this holds great promise cure life-threatening cancers. However, challenges remain determining how best use biomarker therapeutic target. Here we summarize current findings concerning role CD44/CD44v regulation stemness research status biomarkers targets cancer. We also discuss future directions lead clinical applications. Significance Mounting cells (CSCs) mainly responsible aggressiveness, drug resistance, relapse. have been identified surface isolating enriching CSCs different summarized. applications discussed.

Language: Английский

Citations

558
Cancer Stem Cells: The Architects of the Tumor Ecosystem DOI Creative Commons
Briana C. Prager, Qi Xie, Shideng Bao

et al.

Cell stem cell, Journal Year: 2019, Volume and Issue: 24(1), P. 41 - 53

Published: Jan. 1, 2019

Language: Английский

Citations

496
The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis DOI Creative Commons

Yuhe Huang,

Weiqi Hong,

Xiawei Wei

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Sept. 8, 2022

Abstract Epithelial–mesenchymal transition (EMT) is an essential process in normal embryonic development and tissue regeneration. However, aberrant reactivation of EMT associated with malignant properties tumor cells during cancer progression metastasis, including promoted migration invasiveness, increased stemness, enhanced resistance to chemotherapy immunotherapy. tightly regulated by a complex network which orchestrated several intrinsic extrinsic factors, multiple transcription post-translational control, epigenetic modifications, noncoding RNA-mediated regulation. In this review, we described the molecular mechanisms, signaling pathways, stages tumorigenesis involved discussed dynamic non-binary its role metastasis. Finally, summarized challenges immunotherapy proposed strategies for therapy targeting EMT.

Language: Английский

Citations

490
Targeting Cancer Stemness in the Clinic: From Hype to Hope DOI Creative Commons
Caner Saygin, Daniela Matei, Ravindra Majeti

et al.

Cell stem cell, Journal Year: 2018, Volume and Issue: 24(1), P. 25 - 40

Published: Dec. 27, 2018

Language: Английский

Citations

456
Drug Resistance Driven by Cancer Stem Cells and Their Niche DOI Open Access

Marta Prieto‐Vila,

Ryou Takahashi,

Wataru Usuba

et al.

International Journal of Molecular Sciences, Journal Year: 2017, Volume and Issue: 18(12), P. 2574 - 2574

Published: Dec. 1, 2017

Drug resistance represents one of the greatest challenges in cancer treatment. Cancer stem cells (CSCs), a subset within tumor with potential for self-renewal, differentiation and tumorigenicity, are thought to be major cause therapy failure due their considerable chemo- radioresistance, resulting recurrence eventually metastasis. CSCs situated specialized microenvironment termed niche, mainly composed fibroblasts endothelial, mesenchymal immune cells, which also play pivotal roles drug resistance. These neighboring promote molecular signaling pathways required CSC maintenance survival trigger endogenous CSCs. In addition, niche components such as extracellular matrix physically shelter from therapeutic agents. Interestingly, contribute directly bilateral feedback loop manner. Here, we review recent advances study CSCs, especially collective contribution resistance, since increasingly studies suggest that this interaction should considered target strategies.

Language: Английский

Citations

447
Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (Review) DOI Creative Commons
Masaru Katoh

International Journal of Oncology, Journal Year: 2017, Volume and Issue: 51(5), P. 1357 - 1369

Published: Sept. 19, 2017

Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological metabolic reprogramming to adapt tumor microenvironment survive host defense or therapeutic insults. Intra-tumor heterogeneity cancer-cell plasticity give rise resistance recurrence through clonal replacement reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with FGF, Notch, Hedgehog TGFβ/BMP regulate expression functional CSC markers, such as CD44, CD133 (PROM1), EPCAM LGR5 (GPR49). Aberrant canonical non-canonical in human malignancies, including breast, colorectal, gastric, lung, ovary, pancreatic, prostate uterine cancers, leukemia melanoma, are involved survival, bulk-tumor expansion invasion/metastasis. signaling-targeted therapeutics, anti-FZD1/2/5/7/8 monoclonal antibody (mAb) (vantictumab), anti-LGR5 antibody-drug conjugate (ADC) (mAb-mc-vc-PAB-MMAE), anti-PTK7 ADC (PF-06647020), anti-ROR1 mAb (cirmtuzumab), anti-RSPO3 (rosmantuzumab), small-molecule porcupine inhibitors (ETC-159, WNT-C59 WNT974), tankyrase (AZ1366, G007-LK, NVP-TNKS656 XAV939) β-catenin (BC2059, CWP232228, ICG-001 PRI-724), clinical trials preclinical studies treatment patients WNT-driven cancers. therapeutics applicable combination therapy BCR-ABL, EGFR, FLT3, KIT RET treat a subset tyrosine kinase-driven cancers because kinase converge maintenance CSCs. might also be immune checkpoint blockers, atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab pembrolizumab, evasion, although context-dependent effects on immunity should carefully assessed. Omics monitoring, genome sequencing transcriptome tests, immunohistochemical analyses PD-L1 (CD274), PD-1 (PDCD1), ROR1 nuclear organoid-based drug screening, is necessary determine appropriate cancer patients.

Language: Английский

Citations

395