CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer

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

Published: May 7, 2019

Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants regulate colorectal cancer (CRC) metastasis and chemoresistance have not been fully characterized. CAFs NFs were obtained from fresh CRC adjacent normal tissues. Exosomes isolated conditioned medium serum of patients using ultracentrifugation method ExoQuick Exosome Precipitation Solution kit, characterized by transmission electronic microscopy, nanosight western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs exosomes secreted or NFs. The internalization exosomes, transfer miR-92a-3p observed immunofluorescence. Boyden chamber migration invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection primary colon liver assays explore effect NFs, them on epithelial-mesenchymal transition, stemness, chemotherapy resistance CRC. Luciferase report assay, real-time qPCR, blot, immunofluorescence, immunohistochemistry staining regulation miR-92a-3p, FBXW7 MOAP1. promote transition (EMT), cells. Importantly, exert their directly transferring cells, leading a significant increase level Mechanically, increased expression activates Wnt/β-catenin pathway inhibits mitochondrial apoptosis inhibiting MOAP1, contributing EMT, 5-FU/L-OHP Clinically, is significantly tissues negatively correlated with levels MOAP1 specimens, high exosomal highly linked patients. Inhibiting provides an alternative modality for prediction treatment

Language: Английский

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Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: July 14, 2022

Abstract Background The Wnt signaling pathway is a complex network of protein interactions that functions most commonly in embryonic development and cancer, but also involved normal physiological processes adults. canonical regulates cell pluripotency determines the differentiation fate cells during development. (also known as Wnt/β-catenin pathway) recognized driver colon cancer one representative pathways. As functional effector molecule signaling, modification degradation β-catenin are key events progression cancer. Therefore, plays an important role pathogenesis diseases, especially colorectal (CRC). Objective Inhibit to explore therapeutic targets Methods Based on studying pathway, master biochemical related analyze relevant when drugs or inhibitors act clarify medication ideas for treatment Results pathways include: planar polarity (Wnt-PCP) Wnt-Ca 2+ pathway. closely proliferation, stemness, apoptosis, autophagy, metabolism, inflammation immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis. Drugs/phytochemicals molecular preparations CRC have now been developed. used clinically CRC. Conclusion drugs/phytochemicals targeting can effectively treat clinically.

Language: Английский

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Long non-coding RNAs towards precision medicine in gastric cancer: early diagnosis, treatment, and drug resistance

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: May 27, 2020

Gastric cancer is a deadly disease and remains the third leading cause of cancer-related death worldwide. The 5-year overall survival rate patients with early-stage localized gastric more than 60%, whereas that distant metastasis less 5%. Surgical resection best option for cancer, while chemotherapy mainly used in middle advanced stages this disease, despite frequently reported treatment failure due to resistance. Therefore, there an unmet medical need identifying new biomarkers early diagnosis proper management patients, achieve response treatment. Long non-coding RNAs (lncRNAs) body fluids have attracted widespread attention as screening, diagnosis, treatment, prognosis, responses drugs high specificity sensitivity. In present review, we focus on clinical potential lncRNAs liquid biopsies prognosis cancer. We also comprehensively discuss roles their molecular mechanisms chemoresistance well therapeutic targets precision medicine.

Language: Английский

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EMT‐associated microRNAs and their roles in cancer stemness and drug resistance

Cancer Communications, Journal Year: 2021, Volume and Issue: 41(3), P. 199 - 217

Published: Jan. 27, 2021

Abstract Epithelial‐to‐mesenchymal transition (EMT) is implicated in a wide array of malignant behaviors cancers, including proliferation, invasion, and metastasis. Most notably, previou studies have indicated that both cancer stem‐like properties drug resistance were associated with EMT. Furthermore, microRNAs (miRNAs) play pivotal role the regulation EMT phenotype, as result, some miRNAs impact stemness resistance. Therefore, understanding relationship between EMT‐associated stemness/drug beneficial to basic research clinical treatment. In this review, we preliminarily looked into various roles nature cells. Then, reviewed interaction drug‐resistant complex signaling pathways multiple cancers lung cancer, gastric gynecologic breast liver colorectal pancreatic esophageal nasopharyngeal cancer. We finally discussed EMT, stemness, resistance, well forward potential applications miRNA therapy for tumors.

Language: Английский

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Comprehensive analysis of spatial architecture in primary liver cancer

Science Advances, Journal Year: 2021, Volume and Issue: 7(51)

Published: Dec. 17, 2021

Spatial transcriptome technique was applied to decipher the spatial architecture and TME characteristics of liver cancers.

Language: Английский

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Association of the Epithelial–Mesenchymal Transition (EMT) with Cisplatin Resistance

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(11), P. 4002 - 4002

Published: June 3, 2020

Therapy resistance is a characteristic of cancer cells that significantly reduces the effectiveness drugs. Despite popularity cisplatin (CP) as chemotherapeutic agent, which widely used in treatment various types cancer, to CP chemotherapy has been extensively observed. Among reported mechanism(s), epithelial-mesenchymal transition (EMT) process can contribute chemoresistance by converting motionless epithelial into mobile mesenchymal and altering cell-cell adhesion well cellular extracellular matrix, leading invasion tumor cells. By analyzing impact different molecular pathways such microRNAs, long non-coding RNAs, nuclear factor-κB (NF-ĸB), phosphoinositide 3-kinase-related protein kinase (PI3K)/Akt, mammalian target rapamycin (mTOR), Wnt, play an important role exhibited therapy, we first give introduction about EMT mechanism its drug resistance. We then focus specifically on involved pharmacological strategies be mitigate this Overall, highlight targeted signaling could considered future studies pave way for inhibition EMT-mediated displayed response exposure.

Language: Английский

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Mutant p53 in Cancer Progression and Targeted Therapies

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: Nov. 6, 2020

TP53 is the most frequently mutated tumor suppressor gene in human cancer. The majority of mutations p53 are missense mutations, leading to expression full length mutant proteins. Mutant (Mutp53) proteins not only lose wild-type p53-dependent suppressive functions, but also acquire oncogenic gain-of-functions (GOF) that promote tumorigenesis. In this review, we summarize recent advances our understanding GOF mutp53 and potential therapies targeting cancers. particular, discuss promising drugs currently under clinical trials as well emerging therapeutic strategies, including CRISPR/Cas9 based genome edition allele, small peptide mediated restoration function, immunotherapies directly eliminate expressing cells.

Language: Английский

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Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(15), P. 5207 - 5207

Published: July 23, 2020

Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression recurrence after therapy. Effective therapeutic management this disease still remains elusive as evidenced poor patient survival rates. To achieve a more effective regimen, hence survival, there is need to identify focused targeted therapies for OSs treatment the clinical setting. The role OS tumor stroma microenvironment plays significant part development dissemination disease. Important components, potential targets treatment, tumor-infiltrating macrophages that known orchestrate many aspects stromal signaling progression. In particular, increased infiltration M2-like tumor-associated (TAMs) has been associated with metastasis prognosis despite currently used aggressive regimens. This review aims provide summary update current macrophage-centered knowledge discuss possible roles play process focusing on influence cross-talk between TAMs, cancer-stem cells additional tumoral factors.

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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Cancer Stem Cells and Targeting Strategies

Cells, Journal Year: 2019, Volume and Issue: 8(8), P. 926 - 926

Published: Aug. 18, 2019

Chemoresistance is a major problem in cancer therapy as cells develop mechanisms that counteract the effect of chemotherapeutic compounds, leading to relapse and development more aggressive cancers contribute poor prognosis survival rates treated patients. Cancer stem (CSCs) play key role this event. Apart from their slow proliferative property, CSCs have developed range cellular processes involve drug efflux, enzymatic inactivation other mechanisms. In addition, microenvironment where evolve (CSC niche), effectively contributes initiation, progression chemoresistance. CSC niche, immune cells, mesenchymal (MSCs), endothelial associated fibroblasts (CAFs) maintenance malignancy via secretion factors promote resistance chemotherapy. Due these hinder successful therapies, are subject intense research aims at better understanding behaviour developing efficient targeting therapies. review, we provide an overview chemoresistance, discuss progress has been made targeted

Language: Английский

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