Tumor microenvironment heterogeneity an important mediator of prostate cancer progression and therapeutic resistance

npj Precision Oncology, Journal Year: 2022, Volume and Issue: 6(1)

Published: May 4, 2022

Prostate cancer is characterized by a high degree of heterogeneity, which poses major challenge to precision therapy and drug development. In this review, we discuss how nongenetic factors contribute heterogeneity prostate cancer. We also tumor phenotypic switching related anticancer therapies. Lastly, summarize the challenges targeting environments, emphasize that continued exploration needed in order offer personalized for advanced patients.

Language: Английский

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Interplay between Cell Death and Cell Proliferation Reveals New Strategies for Cancer Therapy

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4723 - 4723

Published: April 25, 2022

Cell division and cell death are fundamental processes governing growth development across the tree of life. This relationship represents an evolutionary link between cycle programs that is present in all cells. Cancer characterized by aberrant regulation both, leading to unchecked proliferation replicative immortality. Conventional anti-cancer therapeutic strategies take advantage proliferative dependency cancer yet, doing so, triggering apoptosis, a pathway which inherently resistant. A thorough understanding how therapeutics kill cells needed develop novel, more durable treatment strategies. While evolves cell-intrinsic resistance physiological pathways, there opportunities for agnostic forms death, example, necroptosis or ferroptosis. Furthermore, independent immunogenic, potentially licensing host immunity additional antitumor activity. Identifying vulnerabilities critical developing alternative can overcome resistance.

Language: Английский

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Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3542 - 3542

Published: March 24, 2022

DNA replication during cell proliferation is ‘vertical’ copying, which reproduces an initial amount of genetic information. Polyploidy, results from whole-genome duplication, a fundamental complement to vertical copying. Both organismal and polyploidy can emerge via premature cycle exit or cell-cell fusion, the latter giving rise polyploid hybrid organisms epigenetic hybrids somatic cells. Polyploidy-related increase in biological plasticity, adaptation, stress resistance manifests evolution, development, regeneration, aging, oncogenesis, cardiovascular diseases. Despite prevalence nature importance for medicine, agri- aquaculture, processes mechanisms underlying these features largely remain unknown. The evolutionarily conserved include activation transcription, response stress, damage hypoxia, induction programs morphogenesis, unicellularity, longevity, suggesting that common confer adaptive viability, cells organisms. By increasing polyploidization provide survival under stressful conditions where diploid cannot survive. However, it occurs at expense specific function, thus promoting developmental programming adult diseases risk cancer. Notably, genes arising evolutionary are heavily involved cancer other Ploidy-related changes gene expression presumably originate chromatin modifications derepression bivalent genes. provided evidence elucidates role carcinogenesis, may contribute development new strategies regeneration preventing

Language: Английский

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The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(9), P. 1563 - 1579.e8

Published: Aug. 4, 2023

Language: Английский

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Nuclear morphology predicts cell survival to cisplatin chemotherapy

Neoplasia, Journal Year: 2023, Volume and Issue: 42, P. 100906 - 100906

Published: May 10, 2023

The emergence of chemotherapy resistance drives cancer lethality in patients, with treatment initially reducing overall tumor burden followed by resistant recurrent disease. While molecular mechanisms underlying phenotypes have been explored, less is known about the cell biological characteristics cells that survive to eventually seed recurrence. To identify unique phenotypic associated survival upon exposure, we characterized nuclear morphology and function as prostate recovered following cisplatin treatment. Cells survived days weeks after resisted therapy-induced death showed increasing size size, enabled continuous endocycling resulting repeated whole genome doubling. We further found therapy release were predominantly mononucleated likely employ more efficient DNA damage repair. Finally, show surviving exhibit a distinct nucleolar phenotype increased rRNA levels. These data support paradigm where soon release, treated population mostly contains high level widespread catastrophic leads apoptosis, while minority successful DDR are access pro-survival state. findings consistent accession polyaneuploid (PACC) state, recently described mechanism Our demonstrate fate define key PACC This work essential for understanding and, ultimately, targeting

Language: Английский

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Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(2)

Published: Feb. 1, 2024

Abstract Tumour cell dormancy is critical for metastasis and resistance to chemoradiotherapy. Polyploid giant cancer cells (PGCCs) with or multiple nuclei high DNA content have the properties of stem single PGCCs can individually generate tumours in immunodeficient mice. represent a dormant form that survive harsh tumour conditions contribute recurrence. Hypoxic mimics, chemotherapeutics, radiation cytotoxic traditional Chinese medicines induce formation through endoreduplication and/or fusion. After incubation, recover from treatment produce daughter strong proliferative, migratory invasive abilities via asymmetric division. Additionally, resist hypoxia chemical stress distinct protein signature involves chromatin remodelling cycle regulation. Dormant cellular basis therapeutic resistance, metastatic cascade disease This review summarises regulatory mechanisms governing entry exit dormancy, which may be used by PGCCs, potential strategies targeting PGCCs.

Language: Английский

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Single-Cell Proteomic Characterization of Drug-Resistant Prostate Cancer Cells Reveals Molecular Signatures Associated with Morphological Changes

Molecular & Cellular Proteomics, Journal Year: 2025, Volume and Issue: unknown, P. 100949 - 100949

Published: March 1, 2025

This study delves into the proteomic intricacies of drug-resistant cells (DRCs) within prostate cancer, which are known for their pivotal roles in therapeutic resistance, relapse, and metastasis. Utilizing single-cell proteomics (SCP) with an optimized high-throughput Data Independent Acquisition (DIA) approach throughput 60 sample per day, we characterized landscape DRCs comparison to parental PC3 cells. DIA method allowed robust reproducible protein quantification at level, enabling identification over 1,300 proteins cell on average. Distinct sub-clusters DRC population were identified, closely linked variations size. The uncovered novel signatures, including regulation critical adhesion metabolic processes, as well upregulation surface transcription factors cancer progression. Furthermore, by conducting RNA-seq (scRNA-seq) analysis, identified six upregulated ten downregulated genes consistently altered drug-treated across both SCP scRNA-seq platforms. These findings underscore heterogeneity unique molecular providing valuable insights biological behavior potential targets.

Language: Английский

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Stress-Induced Polyploid Giant Cancer Cells: Unique Way of Formation and Non-Negligible Characteristics

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Aug. 30, 2021

Polyploidy is a conserved mechanism in cell development and stress responses. Multiple stresses of treatment, including radiation chemotherapy drugs, can induce the polyploidization tumor cells. Through endoreplication or fusion, diploid cells convert into giant with single large nuclei multiple small nucleuses. Some stress-induced colossal cells, which were previously thought to be senescent have no ability proliferate, escape fate death by special way. They remain alive at least before producing progeny through asymmetric division, depolyploidization way named neosis. Those danger are recognized as polyploid cancer (PGCCs). Such under suspicion being highly related recurrence metastasis after treatment bring new targets for therapy. However, differences formation mechanisms between PGCCs well-accepted largely unknown. In this review, methods used different studies summarized, several demonstrated. Besides, we discuss some characteristics poor prognosis caused order provide readers more comprehensive understanding these huge

Language: Английский

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The Nuclear-to-Cytoplasmic Ratio: Coupling DNA Content to Cell Size, Cell Cycle, and Biosynthetic Capacity

Annual Review of Genetics, Journal Year: 2022, Volume and Issue: 56(1), P. 165 - 185

Published: Aug. 17, 2022

Though cell size varies between different cells and across species, the nuclear-to-cytoplasmic (N/C) ratio is largely maintained species within types. A maintains a relatively constant N/C by coupling DNA content, nuclear size, size. We explore how couple division growth to content. In some cases, use as molecular yardstick control availability of cycle regulators. other sets limit for biosynthetic capacity. Developmentally programmed variations in given type suggest that specific required respond physiological demands. Recent observations connecting decreased ratios with cellular senescence indicate maintaining proper essential functioning. Together, these findings causative, not simply correlative, role regulating progression.

Language: Английский

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High-Risk Oncogenic Human Cytomegalovirus

Viruses, Journal Year: 2022, Volume and Issue: 14(11), P. 2462 - 2462

Published: Nov. 7, 2022

Human cytomegalovirus (HCMV) is a herpesvirus that infects between 40% and 95% of the population worldwide, usually without symptoms. The host immune response keeps virus in latent stage, although HCMV can reactivate an inflammatory context, which could result sequential lytic/latent viral cycles during lifetime thereby participate genomic diversity humans. high level intra-host variability oncomodulatory role where will favor development spread cancerous cells. Recently, oncogenic has been highlighted directly transform primary cells; such strains are named high-risk (HR) strains. In light these new findings, this review defines criteria characterize HR-HCMV their molecular as well phenotypic impact on infected cell its tumor microenvironment.

Language: Английский

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