Hypoxia-inducible factors: cancer progression and clinical translation

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(11)

Опубликована: Май 31, 2022

Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis that match O2 supply and demand for each the 50 trillion cells in adult human body. Cancer co-opt this homeostatic system to drive cancer progression. HIFs activate transcription thousands genes mediate angiogenesis, stem cell specification, motility, epithelial-mesenchymal transition, extracellular matrix remodeling, glucose lipid metabolism, immune evasion, invasion, metastasis. In Review, mechanisms consequences HIF activation presented. The current status future prospects small-molecule inhibitors use as therapeutics discussed.

Язык: Английский

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The emerging role of photoacoustic imaging in clinical oncology

Nature Reviews Clinical Oncology, Год журнала: 2022, Номер 19(6), С. 365 - 384

Опубликована: Март 23, 2022

Язык: Английский

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Inflammation-Induced Tumorigenesis and Metastasis

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(11), С. 5421 - 5421

Опубликована: Май 21, 2021

Inflammation, especially chronic inflammation, plays a pivotal role in tumorigenesis and metastasis through various mechanisms is now recognized as hallmark of cancer an attractive therapeutic target cancer. In this review, we discuss recent advances molecular how inflammation promotes suppresses anti-tumor immunity types solid tumors, including esophageal, gastric, colorectal, liver, pancreatic well hematopoietic malignancies.

Язык: Английский

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Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer

Journal of Advanced Research, Год журнала: 2021, Номер 37, С. 91 - 106

Опубликована: Окт. 6, 2021

Tumors are usually refractory to anti-cancer therapeutics under hypoxic conditions. However, the underlying molecular mechanism remains be elucidated. Our study intended identify hypoxia inducible lncRNAs and their biological function in gastric cancer (GC). Differentially expressed were determined by microarray analysis between GC cells exposed (1% O2) normoxia (21% for 24 h. The expression level of CBSLR was manipulated several cell lines perform analyses both vitro vivo. We identified a hypoxia-induced lncRNA-CBSLR that protected from ferroptosis, leading chem-resistance. Mechanically, interacted with YTHDF2 form CBSLR/YTHDF2/CBS signaling axis decreased stability CBS mRNA enhancing binding m6A-modified coding sequence (CDS) mRNA. Furthermore, levels, methylation ACSL4 protein reduced, polyubiquitination degradation ACSL4. This, turn, pro-ferroptosis phosphatidylethanolamine (PE) (18:0/20:4) PE (18:0/22:4) content contributed ferroptosis resistance. Notably, is upregulated, whereas downregulated tissues compared matched normal tissues; patients high CBSLR/low levels have worse clinical outcome poorer response chemotherapy. reveals novel how HIF1α/CBSLR modulates ferroptosis/chemoresistance GC, illuminating potential therapeutic targets tumors.

Язык: Английский

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ACSL3 and ACSL4, Distinct Roles in Ferroptosis and Cancers

Cancers, Год журнала: 2022, Номер 14(23), С. 5896 - 5896

Опубликована: Ноя. 29, 2022

The long-chain fatty acyl CoA synthetase (ACSLs) family of enzymes contributes significantly to lipid metabolism and produces acyl-coenzyme A by catalyzing acid oxidation. dysregulation ACSL3 ACSL4, which belong the five isoforms ACSLs, plays a key role in cancer initiation, development, metastasis, tumor immunity may provide several possible therapeutic strategies. Moreover, ACSL4 are crucial for ferroptosis, non-apoptotic cell death triggered accumulation membrane peroxides due iron overload. Here, we present summary current knowledge on their functions various cancers. Research molecular mechanisms involved regulation ferroptosis is critical developing targeted therapies cancer.

Язык: Английский

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Nanoparticle‐Based Photothermal Therapy for Breast Cancer Noninvasive Treatment

Advanced Materials, Год журнала: 2023, Номер unknown

Опубликована: Авг. 10, 2023

Rapid advancements in materials science and nanotechnology, intertwined with oncology, have positioned photothermal therapy (PTT) as a promising noninvasive treatment strategy for cancer. The breast's superficial anatomical location aesthetic significance render breast cancer particularly pertinent candidate the clinical application of PTT following melanoma. This review comprehensively explores research conducted on various types nanoparticles employed elaborates their specific roles mechanisms action. integration existing therapies is scrutinized, underscoring its potential synergistic outcomes. Additionally, underlying consequential modifications to tumor microenvironment after are elaborated from medical perspective. Future directions suggested, an emphasis development integrative platforms that combine multiple therapeutic approaches optimization nanoparticle synthesis enhanced efficacy. goal push boundaries toward comprehensive, clinically applicable

Язык: Английский

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Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10

Molecular Cancer, Год журнала: 2022, Номер 21(1)

Опубликована: Март 29, 2022

Abstract Background Hypoxia has long been considered as a hallmark of solid tumors and is closely associated with tumor progression. Circular RNAs (circRNAs) have identified critical modulator in various cancers. However, the connections between hypoxia circRNAs are largely unknown. Methods Here, we investigated expression profile breast cancer (BC) MCF-7 cells under normoxia using microarray. We novel hypoxia-responsive circRNA named circWSB1, whose pattern, potential diagnostic value prognostic significance were assessed by qRT-PCR situ hybridization. Loss- gain-of-function investigations vivo vitro performed to determine biological functions circWSB1. Mechanistically, chromatin immunoprecipitation dual luciferase reporter assays carried out analyze biogenesis Furthermore, biotin-labeled RNA pull-down, mass spectrometry, immunoprecipitation, fluorescent hybridization, electrophoretic mobility shift, deletion-mapping, co-immunoprecipitation rescue experiments applied investigate interaction circWSB1 Ubiquitin-specific peptidase 10 (USP10) well relationship USP10 p53. Results found that was significantly upregulated BC tissues correlated poor clinical outcomes, which might serve an independent factor for patients. Ectopic promoted proliferation cell vivo. transcriptionally HIF1α response could competitively bind deubiquitinase prevent access p53 cells, leading degradation progression BC. Conclusions Taken together, our findings disclose mechanism hypoxia-inducible interact attenuate mediated stabilization promote BC, providing alternative biomarker therapeutic target

Язык: Английский

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Cancer-associated fibroblasts facilitate premetastatic niche formation through lncRNA SNHG5-mediated angiogenesis and vascular permeability in breast cancer

Theranostics, Год журнала: 2022, Номер 12(17), С. 7351 - 7370

Опубликована: Янв. 1, 2022

Background: Metastasis is the leading cause of death in patients with breast cancer (BC). Primary tumors create a premetastatic niche (PMN) secondary organs for subsequent metastases. Cancer-associated fibroblasts (CAFs) are predominant stromal component tumor microenvironment and serve as major contributor to metastasis. However, function mechanism primary CAFs remain unclear BC. Methods: We investigated expression profiles lncRNAs pairs NFs derived from tissues using lncRNA microarray. The levels lncSNHG5, ZNF281, IGF2BP2, CCL2 CCL5 were assessed by qRT-PCR; protein related genes (e.g., CCL2, CCL5) analyzed western blotting and/or ELISA immortalized clinical samples. Tubule formation three-dimensional sprouting assays tissue fluorescence staining conducted investigate angiogenesis. In vitro permeability assays, trans-endothelial invasion vivo examine vascular permeability. regulatory lncSNHG5 was RNA sequencing, fluorescent situ hybridization, cellular fractionation assay, mass spectrometry, pull-down, immunoprecipitation, gene-specific m6A chromatin dual luciferase reporter assay actinomycin D treatment NFs. Results: LncSNHG5 highly expressed played an essential role promoting angiogenesis leakiness through regulation ZNF281 CAFs. enhanced mRNA stability binding reader IGF2BP2. Enhanced transcriptionally regulated activate P38 MAPK signaling endothelial cells. High associated metastasis poor prognosis BC patients. inhibitors RS102895, marasviroc cenicriviroc inhibited PMN blocking CCL2/CCR2 CCL5/CCR5. lncSNHG5-ZNF281-CCL2/CCL5 axis plays inducing promote Conclusions: Our work demonstrates that its downstream ZNF281-CCL2/CCL5 play crucial may potential targets diagnosis

Язык: Английский

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HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(9)

Опубликована: Май 1, 2022

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and available therapies, including immunotherapies, are ineffective for many patients. HCC characterized by intratumoral hypoxia, increased expression hypoxia-inducible factor 1α (HIF-1α) in diagnostic biopsies associated with patient mortality. Here we report the development 32-134D, low-molecular-weight compound that effectively inhibits gene mediated HIF-1 HIF-2 cells, blocks human mouse tumor growth. In immunocompetent mice bearing Hepa1-6 tumors, addition 32-134D to anti-PD1 therapy rate eradication from 25% 67%. Treated showed no changes appearance, behavior, body weight, hemoglobin, or hematocrit. Compound altered large battery genes encoding proteins mediate angiogenesis, glycolytic metabolism, responses innate adaptive immunity. This led significant immune microenvironment, decreased percentage tumor-associated macrophages myeloid-derived suppressor which evasion, an CD8+ T cells natural killer antitumor Taken together, these preclinical findings suggest combining checkpoint blockade may represent breakthrough HCC.

Язык: Английский

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Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Июль 25, 2024

Abstract Ubiquitination, a pivotal posttranslational modification of proteins, plays fundamental role in regulating protein stability. The dysregulation ubiquitinating and deubiquitinating enzymes is common feature various cancers, underscoring the imperative to investigate ubiquitin ligases deubiquitinases (DUBs) for insights into oncogenic processes development therapeutic interventions. In this review, we discuss contributions ubiquitin–proteasome system (UPS) all hallmarks cancer progress drug discovery. We delve multiple functions UPS oncology, including its regulation cancer-associated pathways, metabolic reprogramming, engagement with tumor immune responses, function phenotypic plasticity polymorphic microbiomes, other essential cellular functions. Furthermore, provide comprehensive overview novel anticancer strategies that leverage UPS, application proteolysis targeting chimeras (PROTACs) molecular glues.

Язык: Английский

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