Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: March 30, 2019

In the last decades, role of microenvironment in tumor progression and therapeutic outcome has gained increasing attention. Cancer-associated fibroblasts (CAFs) have emerged as key players among stromal cells, owing to their abundance most solid tumors diverse tumor-restraining/promoting roles. The interplay between cells neighboring CAFs takes place by both paracrine signals (cytokines, exosomes metabolites) or multifaceted functions surrounding extracellular matrix. Here, we dissect recent identified mechanisms underlying CAF-mediated control therapy resistance, which include induction epithelial-to-mesenchymal transition (EMT), activation survival pathways stemness-related programs metabolic reprogramming cells. Importantly, recently unveiled heterogeneity claims tailored efforts aimed at eradicating specific subset facilitating progression, resistance relapse. However, despite large amount pre-clinical data, much effort is still needed translate CAF-directed anti-cancer strategies from bench clinic.

Language: Английский

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Targeting Cancer Stem Cells: A Strategy for Effective Eradication of Cancer

Cancers, Journal Year: 2019, Volume and Issue: 11(5), P. 732 - 732

Published: May 27, 2019

Cancer stem cells (CSCs) are subpopulations of tumor with the ability to self-renew, differentiate, and initiate maintain growth, they considered be main drivers intra- inter-tumoral heterogeneity. While conventional chemotherapy can eradicate majority non-CSC cells, CSCs often drug-resistant, leading recurrence metastasis. The heterogeneity is challenge in developing CSC-targeting therapy; therefore, we other investigators have focused on novel therapeutic strategies that combine inhibitors CSC-regulating pathways. Encouraging preclinical findings suggested CSC pathway blockade indeed enhance cellular sensitivity non-targeted therapy, this work has led several ongoing clinical trials inhibitors. Our studies bladder cancer lung adenocarcinoma demonstrated a crucial role YAP1, transcriptional regulator genes promote cell survival proliferation, regulating phenotypes. Moreover, using lines patient-derived xenograft models, showed inhibition YAP1 enhances efficacy therapies by attenuating stemness features. In review, summarize for targeting cancers discuss potential challenges approach.

Language: Английский

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Fibronectin in Cancer: Friend or Foe

Cells, Journal Year: 2019, Volume and Issue: 9(1), P. 27 - 27

Published: Dec. 20, 2019

The role of fibronectin (FN) in tumorigenesis and malignant progression has been highly controversial. Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic associated with poor prognosis. Interestingly, matrix deposited the tumor microenvironments (TMEs) promotes but paradoxically related to better Here, we justify how impacts transformation subsequently metastatic progression. Next, try reconcile rationalize seemingly conflicting roles cancer TMEs. Finally, propose future perspectives for potential FN-based therapeutic strategies.

Language: Английский

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Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: March 1, 2021

Cancer is a disease which frequently has poor prognosis. Although multiple therapeutic strategies have been developed for various cancers, including chemotherapy, radiotherapy, and immunotherapy, resistance to these treatments impedes the clinical outcomes. Besides active driven by genetic epigenetic alterations in tumor cells, microenvironment (TME) also reported be crucial regulator tumorigenesis, progression, resistance. Here, we propose that adaptive mechanisms of are closely connected with TME rather than depending on non-cell-autonomous changes response treatment. comprehensive understanding need further investigation fully elucidate resistance, many targeting successful. In this review, report recent advances concerning molecular events important factors involved TME, particularly focusing contributions provide insights into potential methods or translational medicine overcome therapy

Language: Английский

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PTEN Tumor-Suppressor: The Dam of Stemness in Cancer

Cancers, Journal Year: 2019, Volume and Issue: 11(8), P. 1076 - 1076

Published: July 30, 2019

PTEN is one of the most frequently inactivated tumor suppressor genes in cancer. Loss or variation gene/protein levels commonly observed a broad spectrum human cancers, while germline mutations cause inherited syndromes that lead to increased risk tumors. restrains tumorigenesis through different mechanisms ranging from phosphatase-dependent and independent activities, subcellular localization protein interaction, modulating array cellular functions including growth, proliferation, survival, DNA repair, cell motility. The main target phosphatase activity significant growth pro-survival signaling pathway cancer: PI3K/AKT/mTOR. Several shreds evidence shed light on critical role normal cancer stem cells (CSCs) homeostasis, with its loss fostering CSC compartment both solid hematologic malignancies. CSCs are responsible for propagation, metastatic spread, resistance therapy, relapse. Thus, understanding how alterations affect hallmarks could be crucial development successful therapeutic approaches. Here, we discuss findings PTEN-mediated control state. We aim unravel regulation key specific CSCs, such as self-renewal, quiescence/cell cycle, Epithelial-to-Mesenchymal-Transition (EMT), particular focus PTEN-based therapy their exploitation novel approaches treatment.

Language: Английский

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Recent Advances on Cell Culture Platforms for In Vitro Drug Screening and Cell Therapies: From Conventional to Microfluidic Strategies

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(18)

Published: March 11, 2023

Abstract The clinical translations of drugs and nanomedicines depend on coherent pharmaceutical research based biologically accurate screening approaches. Since establishing the 2D in vitro cell culture method, scientific community has improved cell‐based drug assays models. Those advances result more informative biochemical development 3D multicellular models to describe biological complexity better enhance simulation vivo microenvironment. Despite overall dominance conventional macroscopic methods, they present physicochemical operational challenges that impair scale‐up by not allowing a high parallelization, multidrug combination, high‐throughput screening. Their combination complementarity with microfluidic platforms enable microfluidics‐based unequivocal advantages therapies. Thus, this review presents an updated consolidated view miniaturization's physical, chemical, considerations scenario. It clarifies field using gradient‐based microfluidics, droplet‐based printed‐based digital‐based SlipChip, paper‐based microfluidics. Finally, it comparative analysis performance methods life achieve increased precision process.

Language: Английский

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The Roles of Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 in Cancer and Cancer Stem Cells

Stem Cells International, Journal Year: 2018, Volume and Issue: 2018, P. 1 - 15

Published: Jan. 1, 2018

RNA-binding proteins (RBPs) mediate the localization, stability, and translation of target transcripts fine-tune physiological functions encoded. The insulin-like growth factor (IGF) 2 mRNA-binding protein (IGF2BP, IMP) family comprises three RBPs, IGF2BP1, IGF2BP2, IGF2BP3, capable associating with IGF2 other mediating their processing. IGF2BP2 represents least understood member this RBPs; however, it has been reported to participate in a wide range processes, such as embryonic development, neuronal differentiation, metabolism. Its dysregulation is associated insulin resistance, diabetes, carcinogenesis may potentially be powerful biomarker candidate for relevant diseases. This review summarizes structural features, regulation, association cancer stem cells.

Language: Английский

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Differences and similarities between cancer and somatic stem cells: therapeutic implications

Stem Cell Research & Therapy, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 18, 2020

Abstract Over the last decades, cancer survival rate has increased due to personalized therapies, discovery of targeted therapeutics and novel biological agents, application palliative treatments. Despite these advances, tumor resistance chemotherapy radiation rapid progression metastatic disease are still seen in many patients. Evidence shown that stem cells (CSCs), a sub-population share common characteristics with somatic (SSCs), contribute this therapeutic failure. The most critical properties CSCs their self-renewal ability capacity for differentiation into heterogeneous populations cells. Although only constitute low percentage total mass, can regrow mass on own. Initially identified leukemia, have subsequently been found cancers breast, colon, pancreas, brain. Common genetic phenotypic features both SSCs CSCs, including upregulated signaling pathways such as Notch, Wnt, Hedgehog, TGF-β. These play fundamental roles development well control cell fate relevant targeting CSCs. differences expression membrane proteins exosome-delivered microRNAs between also important specifically target cancer. Further research efforts should be directed toward elucidation improve existing therapies generate new clinically

Language: Английский

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Pentadecanoic Acid, an Odd-Chain Fatty Acid, Suppresses the Stemness of MCF-7/SC Human Breast Cancer Stem-Like Cells through JAK2/STAT3 Signaling

Nutrients, Journal Year: 2020, Volume and Issue: 12(6), P. 1663 - 1663

Published: June 3, 2020

Saturated fatty acids possess few health benefits compared to unsaturated acids. However, increasing experimental evidence demonstrates the nutritionally beneficial role of odd-chain saturated in human health. In this study, anti-cancer effects pentadecanoic acid were evaluated breast carcinoma MCF-7/stem-like cells (SC), a cell line with greater mobility, invasiveness, and cancer stem properties parental MCF-7 cells. Pentadecanoic exerted selective cytotoxic MCF-7/SC Moreover, reduced stemness suppressed migratory invasive ability as evidenced by results flow cytometry, mammosphere formation assay, an aldehyde dehydrogenase activity Western blot experiments conducted analyze expression markers—CD44, β-catenin, MDR1, MRP1—and epithelial–mesenchymal transition (EMT) markers—snail, slug, MMP9, MMP2. addition, interleukin-6 (IL-6)-induced JAK2/STAT3 signaling, induced cycle arrest at sub-G1 phase, promoted caspase-dependent apoptosis MCF-7/SC. These findings indicate that can serve novel signaling inhibitor suggest acid-rich food intake during treatments.

Language: Английский

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Tuning Cancer Fate: Tumor Microenvironment's Role in Cancer Stem Cell Quiescence and Reawakening

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Oct. 21, 2020

Cancer cell dormancy is a common feature of human tumors and represents major clinical barrier to the long-term efficacy anticancer therapies. Dormant cancer cells, either in primary or disseminated secondary organs, may reawaken relapse into more aggressive disease. The mechanisms underpinning entry exit strongly resemble those governing stemness, include intrinsic contextual cues. Cellular molecular components tumor microenvironment persistently interact with cells. This dialog highly dynamic, as it evolves over time space, cooperates nets, governs features (like quiescence stemness) fate (survival outgrowth). Therefore, deeper insights biology dormant (stem) cells regulating equilibrium quiescence-versus-proliferation are vital our pursuit find new therapeutic opportunities that prevent from ever recurring. Here, we review discuss microenvironmental regulations its parallels offer view strategies adopted lethal recurrence, by eradicating resident maintaining them state

Language: Английский

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