Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)
Published: Sept. 27, 2024
Language: Английский
Life, Journal Year: 2025, Volume and Issue: 15(1), P. 126 - 126
Published: Jan. 18, 2025
Post-translational modifications (PTMs) of proteins dynamically build the buffering and adapting interface between oncogenic mutations environmental stressors, on one hand, cancer cell structure, functioning, behavior. Aberrant PTMs can be considered as enabling characteristics long they orchestrate all malignant variability in proteome cells, cancer-associated tumor microenvironment (TME). On other enhance anticancer mechanisms tumoral ecosystem or sustain beneficial effects oncologic therapies through degradation inactivation carcinogenic or/and activation tumor-suppressor proteins. In this review, we summarized analyzed a wide spectrum involved regulatory that drive tumorigenesis, genetic instability, epigenetic reprogramming, events metastatic cascade, cytoskeleton extracellular matrix (ECM) remodeling, angiogenesis, immune response, tumor-associated microbiome, metabolism rewiring most important hallmarks cancer. All develop due to proteins, which modulate gene transcription, intracellular signaling, protein size, activity, stability localization, trafficking, secretion, half-life, protein–protein interactions (PPIs). associated with exploited better understand underlying molecular heterogeneous chameleonic disease, find new biomarkers progression prognosis, personalize oncotherapies, discover targets for drug development.
Language: Английский
Citations
2
Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14
Published: March 25, 2024
Protein inhibitors of activated STATs (PIAS) are proteins for cytokine signaling that activate activator-mediated gene transcription. These proteins, as versatile cellular regulators, have been described regulators approximately 60 proteins. Dysregulation PIAS is associated with inappropriate expression promotes oncogenic in multiple cancers. Multiple lines evidence revealed family members show modulated expressions cancer cells. Most frequently reported development PIAS1 and PIAS3. SUMOylation post-translational modifier regulates several machineries. SUMO E3 ligase factor transcription factors tangled cells survival, proliferation, differentiation. Attenuated PIAS-mediated mechanism involved tumorigenesis. This review article provides the PIAS/SUMO role modulation transcriptional control, brief update on their antagonistic function different types particular focus a bonafide therapeutic target to inhibit STAT pathway cancers, summarizes natural activators may ability cure cancer.
Language: Английский
Citations
6
Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)
Published: June 18, 2024
Abstract Background Incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) often leads to local recurrence and distant metastasis of the residual tumor. This is closely linked development a tumor immunosuppressive environment (TIME). In this study, underlying mechanisms potential therapeutic targets involved formation TIME tumors following iRFA were explored. Then, TAK-981-loaded nanocomposite hydrogel was constructed, its effects on investigated. Results study reveals that upregulation small ubiquitin-like modifier 2 ( Sumo2 ) activated SUMOylation intricately tied immunosuppression post-iRFA. Both knockdown inhibiting with TAK-981 activate IFN-1 signaling HCC cells, thereby promoting dendritic cell maturation. Herein, we propose an injectable PDLLA-PEG-PDLLA (PLEL) which incorporates self-assembled BSA nanoparticles for complementary localized treatment after iRFA. The sustained release from curbs expansion notably stimulates cytotoxic lymphocyte-mediated antitumor immune response while maintaining biosafety. Furthermore, resulted widespread elevation PD-L1 levels. Combining blockade therapy synergistically eradicates suppresses tumors. Conclusions These findings underscore TAK-981-based strategy as effective enhance RFA HCC. Graphic
Language: Английский
Citations
5
Cancer Letters, Journal Year: 2024, Volume and Issue: 590, P. 216842 - 216842
Published: April 4, 2024
Language: Английский
Citations
4
Advanced Science, Journal Year: 2024, Volume and Issue: 11(44)
Published: Oct. 8, 2024
Abstract RNA‐modifying proteins, classified as “writers,” “erasers,” and “readers,” dynamically modulate RNA by adding, removing, or interpreting chemical groups, thereby influencing stability, functionality, interactions. To date, over 170 distinct modifications more than 100 enzymes have been identified, with ongoing research expanding these numbers. Although significant progress has made in understanding modification, the regulatory mechanisms that govern proteins themselves remain insufficiently explored. Post‐translational (PTMs) such phosphorylation, ubiquitination, acetylation are crucial modulating function behavior of proteins. However, full extent PTM influence on their role disease development remains to be fully elucidated. This review addresses gaps offering a comprehensive analysis roles PTMs play regulating Mechanistic insights provided into how alter biological processes, contribute cellular function, drive progression. In addition, current landscape is examined, highlighting therapeutic potential targeting for precision medicine. By advancing networks, this seeks facilitate effective strategies inspire future critical area
Language: Английский
Citations
4
Molecules, Journal Year: 2025, Volume and Issue: 30(3), P. 645 - 645
Published: Feb. 1, 2025
BC is the most commonly diagnosed cancer and second leading cause of death among women worldwide. Cellular stress a condition that leads to disrupted homeostasis by extrinsic intrinsic factors. Among other stressors, hypoxia driving force for breast (BC) progression general hallmark solid tumors. Thus, intratumoral an important determinant invasion, metastasis, treatment failure, prognosis, patient mortality. Acquisition epithelial–mesenchymal transition (EMT) phenotype also consequence tumor hypoxia. The cellular response mainly regulated signaling pathway, governed hypoxia-inducible factors (HIFs), HIF1α. HIFs are family transcription (TFs), which induce expression target genes involved in cell survival proliferation, metabolic reprogramming, angiogenesis, resisting apoptosis, metastasis. HIF1α cooperates with large number TFs. In this review, we focused on crosstalk cooperation between TFs BC. We identified cluster TFs, proposed as HIF1α-TF interactome, orchestrates hypoxia, due their post-translational modifications (PTMs), including phosphorylation/dephosphorylation, ubiquitination/deubiquitination, SUMOylation, hydroxylation, acetylation, S-nitrosylation, palmitoylation. PTMs these HIF1α-related drive stability activity, degradation turnover, bidirectional translocation cytoplasm or plasma membrane nucleus cells, well transcription/activation proteins encoded oncogenes inactivation suppressor genes. Consequently, interactome crucial regulatory mechanisms oxygen deprivation cells.
Language: Английский
Citations
0
Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13
Published: Feb. 4, 2025
Gastric cancer (GC) is one of the most common and highly lethal malignant tumors worldwide, its occurrence development are regulated by multiple molecular mechanisms. Post-translational modifications (PTM) forms include ubiquitylation, phosphorylation, acetylation methylation. Emerging research has highlighted lactylation glycosylation. The diverse realm PTM crosstalk linked to many critical signaling events involved in neoplastic transformation, carcinogenesis metastasis. This review provides a comprehensive overview impact on progression GC. Specifically, aberrant have been shown alter proliferation, migration, invasion capabilities GC cells. Moreover, closely associated with resistance chemotherapeutic agents Notably, this also discusses phenomenon crosstalk, highlighting interactions among their roles regulating pathways protein functions. Therefore, in-depth investigation into mechanisms targeted therapeutic strategies hold promise for advancing early diagnosis, treatment, prognostic evaluation GC, offering novel insights future directions.
Language: Английский
Citations
0
Cancers, Journal Year: 2025, Volume and Issue: 17(4), P. 631 - 631
Published: Feb. 13, 2025
Epigenetics encompasses heritable and stable changes in gene expression caused by external chromosomal modifications, without altering the underlying DNA sequence. Epigenetic established during early development maintained through successive cell divisions, play a critical role regulating expression. Post-translational modifications (PTMs) are key aspect of epigenetics essential for modulating protein functionality, as well regulatory cellular processes, including proliferation, differentiation, metabolic pathways, tumorigenic events. Among these, small ubiquitin-related modifier (SUMOylation) system is reversible PTM mechanism that alters target interaction surfaces covalent binding to lysine residues, thereby influencing structure function. Acute myeloid leukemia (AML) highly aggressive malignancy characterized clonal expansion primitive hematopoietic stem cells lineage bone marrow. Despite recent advancements therapeutic strategies an improved understanding leukemogenic patient outcomes remain poor, particularly elderly populations. Consequently, efforts have focused on developing novel agents, co-targeting specific mutations or integrating targeted therapies into combinatorial chemotherapeutic regimens. Emerging evidence suggests SUMOylation plays significant AML pathogenesis treatment response, representing promising advanced disease cases. This review provides brief analysis functional highlights its potential target. We also discuss current knowledge gaps propose directions future research advance precision medicine approaches treatment.
Language: Английский
Citations
0
Advanced Science, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 28, 2025
Abstract Abdominal aortic aneurysm (AAA) is a high‐risk inflammatory disorder. SENP3, SUMO2/3‐specific protease, closely involved in the development of cancer. In this study, aim to explore role SENP3 macrophages AAA. It found that protein expression significantly upregulated both human and murine AAA specimens. negatively regulated by E3 ubiquitin ligase STUB1/CHIP. Furthermore, myeloid‐specific knockout inhibited formation AngII‐ CaCl 2 ‐induced mouse models. deficiency repressed lesion macrophage infiltration response. Mechanistic studies identified Cystathionine Gamma–Lyase (CTH), critical enzyme hydrogen sulfide production, as target mediated exacerbating effects on ferroptosis programs macrophages. SUMO‐3 modification at Lysine 361 promoted CTH stability, whereas de‐SUMOylation facilitated its proteasome‐dependent degradation. Most importantly, it inhibitor counteracted protective effect Additionally, supplementation with ATB346, novel H S‐donating naproxen derivative, prevented mice. These suggest SENP3‐mediated deSUMOylation regulates development. The SENP3/CTH axis therefore an important therapeutic for aneurysmal diseases.
Language: Английский
Citations
0
European Journal of Cancer Care, Journal Year: 2025, Volume and Issue: 2025(1)
Published: Jan. 1, 2025
Background: SUMOylation is a posttranslational protein modification, which involved in tumorigenesis, aggression, metastasis, drug resistance, and prognosis, while the molecular characteristics prognostic values of remain unclear. Methods: The transcriptomic data were downloaded from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO), summary‐level genome‐wide association studies (GWAS) expression quantitative trait locus (eQTL) European ancestry collected. patterns CRC patients, tumor microenvironment (TME) immune cell infiltrating characteristics, biological function therapeutic responses, signatures identified. Mendelian randomization (MR) analysis explored causality between CRC. Results: Three SUMOylation‐related clusters classified, Cluster 2 showed worst survival status, most populations infiltrated cells, responses to anti‐CTLA‐4 anti‐PD‐1 therapies, sensitivity chemotherapy. Nine (NDC1, PPARGC1A, CDKN2A, UHRF2, NUP54, PIAS3, H4C4, CHD3, SUMO2) selected validated as signatures. A predictive nomogram was constructed validated. Finally, NUP54 positive, but PPARGC1A negatively associated with risk Conclusion: This study first comprehensively identified possible biomarkers for treatment
Language: Английский
Citations
0