Hypoxia-inducible factor and cellular senescence in pulmonary aging and disease

Biogerontology, Год журнала: 2025, Номер 26(2)

Опубликована: Фев. 26, 2025

Abstract Cellular senescence and hypoxia-inducible factor (HIF) signaling are crucial in pulmonary aging age-related lung diseases such as chronic obstructive disease idiopathic fibrosis cancer. HIF plays a pivotal role cellular adaptation to hypoxia, regulating processes like angiogenesis, metabolism, inflammation. Meanwhile, leads irreversible cell cycle arrest, triggering the senescence-associated secretory phenotype which contributes inflammation, tissue remodeling, fibrosis. Dysregulation of these pathways accelerates progression by promoting oxidative stress, mitochondrial dysfunction, epigenetic alterations. Recent studies indicate that interact at multiple levels, where can both induce suppress senescence, depending on conditions. While transient activation supports repair stress resistance, dysregulation exacerbates pathologies. Furthermore, emerging evidence suggests targeting could offer new therapeutic strategies mitigate diseases. This review explores intricate crosstalk between mechanisms, shedding light how their interplay influences progression. Additionally, we discuss potential interventions, including senolytic therapies modulators, enhance health longevity.

Язык: Английский

---

Multiple roles for basement membrane proteins in cancer progression and EMT

European Journal of Cell Biology, Год журнала: 2022, Номер 101(2), С. 151220 - 151220

Опубликована: Март 30, 2022

Metastasis or the progression of malignancy poses a major challenge in cancer therapy and is principal reason for increased mortality. The epithelial-mesenchymal transition (EMT) basement membrane (BM) allows cells epithelial phenotype to transform into mesenchymal-like (quasi-mesenchymal) metastasize via lymphovascular system through metastatic cascade by intravasation extravasation. This helps carcinoma from primary site distant organs. Collagen, laminin, integrin are prime components BM help tumor cell metastasis, which makes them ideal drug targets. Further, recent studies have shown that collagen, can be used as biomarker cells. In this review, we summarized current knowledge such therapeutics, either currently preclinical clinical stages could promising therapeutics. DATA AVAILABILITY: Not applicable.

Язык: Английский

---

The role of N-glycosylation in cancer

Acta Pharmaceutica Sinica B, Год журнала: 2023, Номер 14(3), С. 1098 - 1110

Опубликована: Окт. 27, 2023

Despite advances in understanding the development and progression of cancer recent years, there remains a lack comprehensive characterization glycoproteome. Glycoproteins play an important role medicine are involved various human disease conditions including cancer. Glycan-moieties participate fundamental processes like cell signaling, invasion, angiogenesis, metastasis. Aberrant

Язык: Английский

---

Learn from antibody–drug conjugates: consideration in the future construction of peptide-drug conjugates for cancer therapy

Experimental Hematology and Oncology, Год журнала: 2022, Номер 11(1)

Опубликована: Ноя. 8, 2022

Cancer is one of the leading causes death worldwide due to high heterogeneity. Although chemotherapy remains mainstay cancer therapy, non-selective toxicity and drug resistance mono-chemotherapy incur broad criticisms. Subsequently, various combination strategies have been developed improve clinical efficacy, also known as cocktail therapy. However, conventional "cocktail administration" just passable, potential toxicities normal tissues unsatisfactory synergistic effects, especially for combined drugs with different pharmacokinetic properties. The conjugates through coupling chemotherapeutics a carrier (such antibody peptide) provide an alternative strategy therapeutic efficacy simultaneously reduce unspecific toxicities, by virtue advantages highly specific targeting ability potent killing effect. 14 antibody-drug (ADCs) approved more are being investigated in trials so far, several limitations disclosed during application. Compared ADCs, peptide-drug (PDCs) possess advantages, including easy industrial synthesis, low cost, tissue penetration fast clearance. So only handful PDCs approved, highlighting tremendous development potential. Herein, we discuss progress pitfalls ADCs underline what can learn from better construction future.

Язык: Английский

---

Ferroptosis and EMT: key targets for combating cancer progression and therapy resistance

Cellular and Molecular Life Sciences, Год журнала: 2023, Номер 80(9)

Опубликована: Авг. 19, 2023

Abstract Iron-dependent lipid peroxidation causes ferroptosis, a form of regulated cell death. Crucial steps in the formation ferroptosis include accumulation ferrous ions (Fe 2+ ) and peroxidation, which are controlled by glutathione peroxidase 4 (GPX4). Its crucial role stopping spread cancer has been shown numerous studies undertaken last ten years. Epithelial–mesenchymal transition (EMT) is process epithelial cells acquire mesenchymal characteristics. EMT connected to carcinogenesis, invasiveness, metastasis, therapeutic resistance cancer. It range internal external signals changes phenotype from like. Studies have that tend be more ferroptotic than their counterparts. Drug-resistant easily killed inducers when they undergo EMT. Therefore, understanding interaction between will help identify novel treatment targets. In-depth discussion given regulation potential application cancer, relationships EMT, signaling pathways associated with tumors. Invasion, inflammation all The goal this review provide suggestions for future research practical guidance applying clinical practice.

Язык: Английский

---

Harnessing epithelial-mesenchymal plasticity to boost cancer immunotherapy

Cellular and Molecular Immunology, Год журнала: 2023, Номер 20(4), С. 318 - 340

Опубликована: Фев. 24, 2023

Abstract Immune checkpoint blockade (ICB) therapy is a powerful option for cancer treatment. Despite demonstrable progress, most patients fail to respond or achieve durable responses due primary acquired ICB resistance. Recently, tumor epithelial-to-mesenchymal plasticity (EMP) was identified as critical determinant in regulating immune escape and immunotherapy resistance cancer. In this review, we summarize the emerging role of EMP tumor-intrinsic extrinsic mechanisms by which tumors exploit immunosuppression escape. We discuss strategies modulate alleviate enhance efficiency therapy. Our discussion provides new prospects response therapeutic gain patients.

Язык: Английский

---

Lantern-shaped flexible RNA origami for Smad4 mRNA delivery and growth suppression of colorectal cancer

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Март 10, 2023

Abstract mRNA delivery has shown high application value in the treatment of various diseases, but its effective is still a major challenge at present. Herein, we propose lantern-shaped flexible RNA origami for delivery. The composed target scaffold and only two customized RGD-modified circular staples, which can compress into nanoscale facilitate endocytosis by cells. In parallel, structure allows large regions to be exposed translated, exhibiting good balance between translation efficiency. context tumor suppressor gene, Smad4 colorectal cancer models demonstrates promising potential accurate manipulation protein levels vitro vivo settings. This strategy provides competitive method mRNA-based therapies.

Язык: Английский

---

Chordoma recruits and polarizes tumor-associated macrophages via secreting CCL5 to promote malignant progression

Journal for ImmunoTherapy of Cancer, Год журнала: 2023, Номер 11(4), С. e006808 - e006808

Опубликована: Апрель 1, 2023

Background Chordoma is an extremely rare, locally aggressive malignant bone tumor originating from undifferentiated embryonic remnants. There are no effective therapeutic strategies for chordoma. Herein, we aimed to explore cellular interactions within the chordoma immune microenvironment and provide new targets. Methods Spectrum flow cytometry multiplex immunofluorescence (IF) staining were used investigate of Cell Counting Kit-8, Edu, clone formation, Transwell, healing assays validate functions. Flow Transwell analyze macrophage phenotype chemotaxis alterations. Immunohistochemistry, IF, western blot, PCR, ELISA molecular expression. An organoid model a xenograft mouse constructed efficacy maraviroc (MVC). Results The landscape was characterized, observed that exhibits typical exclusion phenotype. However, macrophages infiltrating zone also noted. Through functional assays, demonstrated chordoma-secreted CCL5 significantly promoted malignancy progression, recruitment, M2 polarization. In turn, markedly enhanced proliferation, invasion, migration viability knockdown MVC (CCL5/CCR5 inhibitor) treatment both inhibited progression We established patient-derived organoids, wherein exhibited antitumor effects, especially in patient 4, with robust killing effect. inhibits growth lung metastasis vivo. Conclusions Our study implicates CCL5–CCR5 axis plays important role regulation macrophages, potential target

Язык: Английский

---

Mechanotransduction and epigenetic modulations of chromatin: Role of mechanical signals in gene regulation

Journal of Cellular Biochemistry, Год журнала: 2024, Номер 125(3)

Опубликована: Фев. 12, 2024

Abstract Mechanical forces may be generated within a cell due to tissue stiffness, cytoskeletal reorganization, and the changes (even subtle) in cell's physical surroundings. These of impose mechanical tension intracellular protein network (both cytosolic nuclear). could released by series protein–protein interactions often facilitated membrane lipids, lectins sugar molecules thus generate type signal drive cellular processes, including differentiation, polarity, growth, adhesion, movement, survival. Recent experimental data have accentuated molecular mechanism this transduction pathway, dubbed mechanotransduction. Mechanosensitive proteins plasma discern channel information interior. Cells respond message altering their arrangement directly transmitting nucleus through connection cytoskeleton nucleoskeleton before despatched biochemical signaling pathways. Nuclear transmission force leads activation chromatin modifiers modulation epigenetic landscape, inducing reorganization gene expression regulation; time chemical messengers (transcription factors) arrive into nucleus. While significant research has been done on role mechanotransduction tumor development cancer progression/metastasis, mechanistic basis force‐activated carcinogenesis is still enigmatic. Here, review, we discussed various cues connections better comprehend also explored detailed some multiple players (proteins macromolecular complexes) involved Thus, described an avenue: how stress directs modulate epigenome cells aberrant phenotype.

Язык: Английский

---

Remodeling tumor microenvironment by versatile nanoplatform orchestrated mechanotherapy with chemoimmunotherapy to synergistically enhance anticancer efficiency

Biomaterials, Год журнала: 2025, Номер 317, С. 123104 - 123104

Опубликована: Янв. 10, 2025

Язык: Английский

---