Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis

Cancers, Год журнала: 2021, Номер 13(19), С. 4985 - 4985

Опубликована: Окт. 5, 2021

Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype mesenchymal to invade surrounding tissues. EMT physiological event during embryogenesis (type I) but also happens fibrosis II) and cancer metastasis III). It multifaceted phenomenon governed by activation genes associated with cell migration, extracellular matrix degradation, DNA repair, angiogenesis. The employ acquire ability migrate, resist therapeutic agents escape immunity. One key biomarkers vimentin, type III intermediate filament that normally expressed in upregulated metastasis. This review highlights pivotal role vimentin explains its as downstream well an upstream regulator this highly complex process. areas require further research exploring EMT. As cytoskeletal protein, filaments support mechanical integrity migratory machinery, generation directional force, focal adhesion modulation attachment. viscoelastic scaffold, it gives stress-bearing flexible organelles. However, modulates for inducers such Snail, Slug, Twist ZEB1/2, epigenetic factors. In addition, suppresses cellular differentiation upregulates their pluripotent potential inducing self-renewability, thus increasing stemness stem cells, facilitating tumour spread making them more resistant treatments. Several missense frameshift mutations reported human cancers may contribute towards metastatic spread. Therefore, we propose should be target using technologies will curb growth reduced mortality morbidity.

Язык: Английский

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Targeting epigenetic regulators to overcome drug resistance in cancers

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Фев. 17, 2023

Abstract Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic mechanisms, DNA methylation, histone modification, non-coding RNA have been well studied. Increasing evidence has shown that aberrant regulations contribute to tumor resistance. Therefore, targeting regulators represents an effective strategy reverse drug In this review, we summarize roles addition, as essential factors modifications, demethylases mediate or genomic modifications. Herein, comprehensively describe functions demethylase family including lysine-specific family, Jumonji C-domain-containing arginine fully discuss their regulatory mechanisms related therapeutic strategies, small-molecule inhibitors small interfering overcome resistance, are also described.

Язык: Английский

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Revealing the transcriptional heterogeneity of organ‐specific metastasis in human gastric cancer using single‐cell RNA Sequencing

Clinical and Translational Medicine, Год журнала: 2022, Номер 12(2)

Опубликована: Фев. 1, 2022

Abstract Background Deciphering intra‐ and inter‐tumoural heterogeneity is essential for understanding the biology of gastric cancer (GC) its metastasis identifying effective therapeutic targets. However, characteristics different organ‐tropism metastases GC are largely unknown. Methods Ten fresh human tissue samples from six patients, including primary tumour adjacent non‐tumoural organs or tissues (liver, peritoneum, ovary, lymph node) were evaluated using single‐cell RNA sequencing. Validation experiments performed histological assays bulk transcriptomic datasets. Results Malignant epithelial subclusters associated with invasion features, intraperitoneal propensity, epithelial–mesenchymal transition‐induced stem cell phenotypes, dormancy‐like discovered. High expression first three subcluster‐associated genes displayed worse overall survival than those low in a cohort containing 407 samples. Immune stromal cells exhibited cellular created pro‐tumoural immunosuppressive microenvironment. Furthermore, 20‐gene signature node‐derived exhausted CD8 + T was acquired to forecast node validated cohorts. Additionally, although anti‐NKG2A (KLRC1) antibody have not been used treat patients even clinical trials, we uncovered only malignant but one endothelial subcluster, mucosal‐associated invariant cells, cell‐like B plasmacytoid dendritic macrophages, monocytes, neutrophils may contribute HLA‐E‐KLRC1/KLRC2 interaction cytotoxic/exhausted and/or natural killer (NK) suggesting novel opportunities GC. our findings suggested that PD‐1 might predict responses blockade therapy Conclusions This study provided insights into heterogeneous microenvironment tumours organ‐specific provide support precise diagnosis treatment.

Язык: Английский

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The Promise of Nanotechnology in Personalized Medicine

Journal of Personalized Medicine, Год журнала: 2022, Номер 12(5), С. 673 - 673

Опубликована: Апрель 22, 2022

Both personalized medicine and nanomedicine are new to medical practice. Nanomedicine is an application of the advances nanotechnology in being integrated into diagnostic therapeutic tools manage array conditions. On other hand, medicine, which also referred as precision a novel concept that aims individualize/customize management based on personal attributes patient overcome blanket treatment only efficient subset patients, leaving others with either ineffective or results significant toxicity. Novel nanomedicines have been employed several diseases, can be adapted each patient-specific case according their genetic profiles. In this review, we discuss both areas intersection between two emerging scientific domains. The review focuses current situation advantages offered by nanoconstructs diagnosis variability identify right drug for patient. Finally, touch upon challenges fields towards translation nano-personalized medicine.

Язык: Английский

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Insights on functionalized carbon nanotubes for cancer theranostics

Journal of Nanobiotechnology, Год журнала: 2021, Номер 19(1)

Опубликована: Дек. 16, 2021

Abstract Despite the exciting breakthroughs in medical technology, cancer still accounts for one of principle triggers death and conventional therapeutic modalities often fail to attain an effective cure. Recently, nanobiotechnology has made huge advancement therapy with gigantic application potential because their ability achieving precise controlled drug release, elevating solubility reducing adverse effects. Carbon nanotubes (CNTs), most promising carbon-related nanomaterials, have already achieved much success biomedical field. Due excellent optical property, thermal electronic conductivity, easy functionalization high loading capacity, CNTs can be applied a multifunctional way treatment diagnosis. In this review, we will give overview recent progress CNT-based delivery systems theranostics, which emphasizes targetability intracellular components tumor cells extracellular elements microenvironment. Moreover, detailed introduction on how penetrate inside reach sites action achieve effects, as well diagnostic applications highlighted. Graphic

Язык: Английский

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Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Cancers, Год журнала: 2022, Номер 14(4), С. 976 - 976

Опубликована: Фев. 15, 2022

Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal cells, i.e., self-renewal differentiation potential, suggesting they can drive progression. Consequently, targeting to prevent tumor growth or regrowth might offer chance lead the fight against cancer. create their niche, specific area within tissue unique microenvironment sustains vital functions. Interactions between niches play critical role regulating CSCs' tumorigenesis. Differences observed frequency CSCs, due phenotypic plasticity many remain challenge therapeutics, since modulate transcriptional activities into more stem-like state protect themselves from destruction. This represents an essential step future therapeutic approaches. Regarding self-renewal, are modulated by same molecular pathways found such as Wnt/β-catenin signaling, Notch Hedgehog signaling. Another key characteristic resistance standard chemotherapy radiotherapy treatments, capacity rest quiescent state. review will analyze primary mechanisms involved CSC tumorigenesis, particular attention roles progression benign malignant diseases; examine perspectives on identification new markers better control well dissecting process.

Язык: Английский

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An Epigenetic Role of Mitochondria in Cancer

Cells, Год журнала: 2022, Номер 11(16), С. 2518 - 2518

Опубликована: Авг. 13, 2022

Mitochondria are not only the main energy supplier but also cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD+, and O-linked beta-N-acetylglucosamine (O-GlcNAc), which substrates for DNA methylation histone post-translation modifications, essential gene transcriptional regulation fate determination. Tumorigenesis is attributed to many factors, including mutations tumor microenvironment. initiation, evolution, metastasis, recurrence. Targeting mitochondrial metabolism promising therapeutic strategies treatment. In this review, we summarize of mitochondria required modification discuss current strategy cancer therapies via targeting epigenetic modifiers related enzymes This review an important contribution understanding metabolic-epigenetic-tumorigenesis concept.

Язык: Английский

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Unveiling the mechanisms and challenges of cancer drug resistance

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Фев. 12, 2024

Abstract Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer strategies are evolving due to innate acquired capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells survive progress under unfavorable conditions. Although the mechanism of drug being widely studied generate new target-based drugs with better potency than existing ones. However, broader flexibility in resistance, advanced therapeutic options efficacy need be explored. Combination therapy an alternative a success rate though risk amplified side effects commonplace. Moreover, recent groundbreaking precision immune ways overcome has revolutionized anticancer greater extent only limitation individual-specific needs further attention. This review will focus on challenges opted withstand current therapies at molecular level also highlights emerging -like immunological, stem cell-based may prove have potential challenge problem resistance.

Язык: Английский

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Characteristics of the cancer stem cell niche and therapeutic strategies

Stem Cell Research & Therapy, Год журнала: 2022, Номер 13(1)

Опубликована: Июнь 3, 2022

Distinct regions harboring cancer stem cells (CSCs) have been identified within the microenvironment of various tumors, and as in case their healthy counterparts, these anatomical are termed "niche." Thus far, a large volume studies shown that CSC niches take part maintenance, regulation renewal, differentiation plasticity CSCs. In this review, we summarize discuss latest findings regarding niche morphology, physical terrain, main signaling pathways interactions them. The cellular molecular components CSCs also involve genetic epigenetic modulations mediate support ultimately leading to progression. It suggests crosstalk between plays an important role therapy resistance recurrence. addition, updated diverse therapeutic strategies different cancers basic research clinical trials review. Understanding complex heterogeneity is necessary pre-requisite for designing superior target CSC-specific factors and/or niche.

Язык: Английский

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Cancer metastasis: Molecular mechanisms and clinical perspectives

Pharmacology & Therapeutics, Год журнала: 2023, Номер 250, С. 108522 - 108522

Опубликована: Сен. 1, 2023

Язык: Английский

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