EMT mechanism in breast cancer metastasis and drug resistance: Revisiting molecular interactions and biological functions

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 155, P. 113774 - 113774

Published: Oct. 3, 2022

One of the malignant tumors in women that has involved both developed and developing countries is breast cancer. Similar to other types tumors, cancer cells demonstrate high metastatic nature. Besides, tumor have ability drug resistance. EMT related mechanism metastasis focus current manuscript highlighting function malignancy Breast increase their migration by induction During EMT, N-cadherin vimentin levels increase, E-cadherin decrease mediate EMT-induced invasion. Different kinds anti-cancer agents such as tamoxifen, cisplatin paclitaxel mediates chemoresistance feature cells. Furthermore, correlates with radio-resistance tumor. Clinical aspect reversing preventing chemotherapy or radiotherapy failure patients improving survival time. The anti-tumor suppress can be used for decreasing invasion increasing chemosensitivity lncRNAs, miRNAs factors modulate progression are discussed here.

Language: Английский

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How important is EMT for cancer metastasis?

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(2), P. e3002487 - e3002487

Published: Feb. 7, 2024

Epithelial-to-mesenchymal transition (EMT), a biological phenomenon of cellular plasticity initially reported in embryonic development, has been increasingly recognized for its importance cancer progression and metastasis. Despite tremendous progress being made the past 2 decades our understanding molecular mechanism functional EMT cancer, there are several mysteries around that remain unresolved. In this Unsolved Mystery, we focus on variety types metastasis, cooperative collective behaviors, spatiotemporal characterization EMT, strategies therapeutically targeting EMT. We also highlight new technical advances will facilitate efforts to elucidate unsolved

Language: Английский

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Multi-stage mechanisms of tumor metastasis and therapeutic strategies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 11, 2024

The cascade of metastasis in tumor cells, exhibiting organ-specific tendencies, may occur at numerous phases the disease and progress under intense evolutionary pressures. Organ-specific relies on formation pre-metastatic niche (PMN), with diverse cell types complex interactions contributing to this concept, adding a new dimension traditional cascade. Prior metastatic dissemination, as orchestrators PMN formation, primary tumor-derived extracellular vesicles prepare fertile microenvironment for settlement colonization circulating cells distant secondary sites, significantly impacting cancer progression outcomes. Obviously, solely intervening sites passively after macrometastasis is often insufficient. Early prediction holistic, macro-level control represent future directions therapy. This review emphasizes dynamic intricate systematic alterations that progresses, illustrates immunological landscape creation, deepens understanding treatment modalities pertinent metastasis, thereby identifying some prognostic predictive biomarkers favorable early predict occurrence design appropriate combinations.

Language: Английский

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Design of PD‐L1‐Targeted Lipid Nanoparticles to Turn on PTEN for Efficient Cancer Therapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(22)

Published: March 23, 2024

Abstract Lipid nanoparticles (LNPs) exhibit remarkable mRNA delivery efficiency, yet their majority accumulate in the liver or spleen after injection. Tissue‐specific can be achieved through modulating LNP properties, such as tuning PEGylation varying lipid components systematically. In this paper, a streamlined method is used for incorporating tumor‐targeting peptides into LNPs; programmed death ligand 1 (PD‐L1) binding are conjugated to PEGylated lipids via copper‐free click reaction, and directly incorporated composition (Pep LNPs). Notably, Pep LNPs display robust interaction with PD‐L1 proteins, which leads uptake of overexpressing cancer cells both vitro vivo. To evaluate anticancer immunotherapy mediated by restoring tumor suppressor, encoding phosphatase tensin homolog (PTEN) delivered PTEN‐deficient triple‐negative breast cancers (TNBCs). loaded PTEN specifically promotes autophagy‐mediated immunogenic cell 4T1 tumors, resulting effective immune responses. This study highlights potential tumor‐targeted mRNA‐based therapy.

Language: Английский

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The temporal progression of lung immune remodeling during breast cancer metastasis

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(6), P. 1018 - 1031.e6

Published: May 30, 2024

Language: Английский

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Triple-Negative Breast Cancer Progression and Drug Resistance in the Context of Epithelial–Mesenchymal Transition

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 228 - 228

Published: Jan. 12, 2025

Triple-negative breast cancer (TNBC) is one of the most difficult subtypes to treat due its distinct clinical and molecular characteristics. Patients with TNBC face a high recurrence rate, an increased risk metastasis, lower overall survival compared other subtypes. Despite advancements in targeted therapies, traditional chemotherapy (primarily using platinum compounds taxanes) continues be standard treatment for TNBC, often limited long-term efficacy. tumors are heterogeneous, displaying diverse mutation profile considerable chromosomal instability, which complicates therapeutic interventions. The development chemoresistance frequently associated process epithelial–mesenchymal transition (EMT), during epithelial tumor cells acquire mesenchymal-like phenotype. This shift enhances metastatic potential, while simultaneously reducing effectiveness chemotherapeutics. It has also been suggested that EMT plays central role stem cells. Hence, there growing interest exploring small-molecule inhibitors target as future strategy overcoming resistance improving outcomes patients TNBC. review focuses on progression drug emphasis these processes. We present TNBC-specific EMT-related features, key protein markers, various signaling pathways involved. discuss important mechanisms factors related within context EMT, highlighting improve patients’ outcomes.

Language: Английский

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Dissecting metastasis using preclinical models and methods

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(6), P. 391 - 407

Published: May 3, 2023

Language: Английский

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Disheveled3 enhanced EMT and cancer stem-like cells properties via Wnt/β-catenin/c-Myc/SOX2 pathway in colorectal cancer

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 5, 2023

Epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSLCs) play crucial role in tumor metastasis drug-resistance. Disheveled3 (DVL3) is involved malignant behaviors of cancer. However, the potential mechanism DVL3 remain elusive EMT CSLCs colorectal (CRC).

Language: Английский

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Stabilization of E-cadherin adhesions by COX-2/GSK3β signaling is a targetable pathway in metastatic breast cancer

JCI Insight, Journal Year: 2023, Volume and Issue: 8(6)

Published: Feb. 9, 2023

Metastatic progression of epithelial cancers can be associated with epithelial-mesenchymal transition (EMT) including transcriptional inhibition E-cadherin (CDH1) expression. Recently, EM plasticity (EMP) and E-cadherin-mediated, cluster-based metastasis treatment resistance have become more appreciated. However, the mechanisms that maintain expression in this context are less understood. Through studies inflammatory breast cancer (IBC) a 3D tumor cell "emboli" culture paradigm, we discovered cyclooxygenase 2 (COX-2; PTGS2), target gene C/EBPδ (CEBPD), or its metabolite prostaglandin E2 (PGE2) promotes protein stability E-cadherin, β-catenin, p120 catenin through GSK3β. The COX-2 inhibitor celecoxib downregulated complex proteins caused death. Coexpression was seen tissues from patients poor outcome and, along inhibitory GSK3β phosphorylation, patient-derived xenografts (PDX) triple negative (TNBC).Celecoxib alone decreased within xenograft tumors, though CDH1 mRNA levels increased, reduced circulating (CTC) clusters. In combination paclitaxel, attenuated regressed lung metastases. This study has uncovered mechanism by which metastatic cells E-cadherin-mediated cell-to-cell adhesions survival, suggesting some COX-2+/E-cadherin+ may benefit targeting PGE2 signaling pathway.

Language: Английский

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Impact of platelet-derived mitochondria transfer in the metabolic profiling and progression of metastatic MDA-MB-231 human triple-negative breast cancer cells

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 12, 2024

Introduction: An active role of platelets in the progression triple-negative breast cancer (TNBC) cells has been described. Even platelet-derived extracellular vesicles on migration MDA-MB-231 reported. Interestingly, upon activation, release functional mitochondria into environment. However, impact these metabolic properties remains unclear. Methods: and MDA-MB-231-Rho-0 were co-cultured with platelets, which isolated from donor blood. Mitochondrial transfer was assessed through confocal microscopy flow cytometry, while analyses conducted using a Seahorse XF HS Mini Analyzer. The mito-chondrial DNA (mtDNA) copy number determined via quantitative PCR (qPCR) following platelet co-culture. Finally, cell proliferation colony formation assay performed crystal violet staining. Results Discussion: We have shown that are internalized by co-culture increasing ATP production, oxygen (O 2 ) consumption rate (OCR), proliferation, adaptability. Additionally, we observed depleted mtDNA restore uridine/pyruvate-free culture medium mitochondrial O after indicating reconstitution facilitated mitochondria. In conclusion, our study provides new insights adaptability metastatic TNBC cells.

Language: Английский

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