The Druggable Target Potential of NF-κB-Inducing Kinase (NIK) in Cancer DOI Creative Commons
Yina Wang, Liangyou Rui

International Journal of Translational Medicine, Год журнала: 2024, Номер 5(1), С. 1 - 1

Опубликована: Дек. 25, 2024

NF-κB-inducing kinase (NIK) is primarily recognized for its role as the apical that activates non-canonical NF-κB signaling and involvement in immune system regulation. NIK crucial maintaining cellular health by regulating fundamental processes such differentiation, growth, survival. Emerging evidence suggests dysregulated expression or function of non-lymphoid cells a key factor cancer progression. While deficiency causes severe dysfunction, overexpression excessive activation linked to inflammatory diseases, metabolic disorders, development. The development small molecule inhibitors targeting has sparked optimism clinical intervention, positioning promising druggable mediator cancer. ongoing progress creating novel offers new opportunities testing NIK-targeted therapies, potentially advancing application NIK-based treatments.

Язык: Английский

Interactomic exploration of LRRC8A in volume-regulated anion channels DOI Creative Commons
Veronica Carpanese, Margherita Festa, Elena Prosdocimi

и другие.

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Июнь 22, 2024

Abstract Ion channels are critical in enabling ion movement into and within cells important targets for pharmacological interventions different human diseases. In addition to their transport abilities, interact with signalling scaffolding proteins, which affects function, cellular positioning, links intracellular pathways. The study of “channelosomes” has the potential uncover involvement diseases, although this field research is still emerging. LRRC8A gene that encodes a crucial protein involved formation volume-regulated anion (VRACs). Some studies suggest could be valuable prognostic tool types cancer, serving as biomarker predicting patients’ outcomes. expression levels might linked tumour progression, metastasis, treatment response, its implications cancer can varied. Here, publicly accessible databases patients were systematically analysed determine if correlation between VRAC channel survival rate exists across distinct types. Moreover, we re-evaluated impact on proliferation migration colon via HCT116 LRRC8A-KO cells, current topic debate literature. addition, investigate role signalling, conducted biotin proximity-dependent identification (BioID) analysis, revealing cell-cell junctions, mechanisms govern calcium homeostasis, kinases, GTPase signalling. Overall, dataset improves our understanding LRRC8A/VRAC explores new avenues while identifying promising therapeutic promoting inventive methods disease treatment.

Язык: Английский

Процитировано

6

Volume-regulated anion channels conduct ATP in undifferentiated mammary cells and promote tumorigenesis in xenograft nude mouse DOI Creative Commons
Kishio Furuya, Hiroaki Hirata, Takeshi Kobayashi

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 12

Опубликована: Янв. 15, 2025

The high interstitial ATP concentration in the cancer microenvironment is a major source of adenosine, which acts as strong immune suppressor. However, release has not been elucidated. We measured during hypotonic stress using real-time luminescence imaging system breast cell lines and primary cultured mammary cells. In lines, was released with slowly rising diffuse pattern, whereas cells, intermittently transient-sharp peaks. pattern changed to by cholera toxin treatment reverse change induced transforming growth factor (TGF) β treatment. DCPIB, an inhibitor volume-regulated anion channels (VRACs), suppressed pattern. inflammatory mediator sphingosine-1-phosphate (S1P) isovolumetrically. Knockdown A isoform leucine-rich repeat-containing protein 8 (LRRC8A), essential molecular entity VRACs, shRNA nude mouse xenograft model, LRRC8A knockdown tumorigenesis subcutaneously implanted These results suggest that abundantly expressed VRACs are conduit undifferentiated including

Язык: Английский

Процитировано

0

Recent insights on the impact of SWELL1 on metabolic syndromes DOI Creative Commons
Mei Qin, Xuejie Yi,

Zhi-Jian Duan

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 21, 2025

SWELL1 is a key component of the volume-regulated anion channel (VRAC) and participates in cell volume regulation as an ion plasma membrane protein. While early studies focused on its role immune development tumor progression, recent have revealed that plays important metabolic diseases. Studies shown extensively involved physiological processes peripheral tissues, including adipocyte hypertrophy, skeletal muscle regulation, insulin secretion, hepatic lipid metabolism through interactions with signaling pathway. These functions play roles pathogenesis obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), suggesting may be new target for treatment In this review, we focus structural functional characteristics to provide in-depth explanation syndrome, especially pathway, basis therapeutic strategies diseases targeting SWELL1.

Язык: Английский

Процитировано

0

Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities DOI
Alicia Llorente Lope, Gurpreet K. Arora, Rabi Murad

и другие.

Nature reviews. Cancer, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Язык: Английский

Процитировано

0

In silico pan-cancer analysis of VRAC subunits and their prognostic roles in human cancers DOI Creative Commons
Alessandro Paolì,

Soha Sadeghi,

Giulia Battistello

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 11, 2025

Язык: Английский

Процитировано

0

Identification of vitamin D-related signature for predicting the clinical outcome and immunotherapy response in hepatocellular carcinoma DOI Creative Commons

Tianyi Wang,

Lulu Han,

Jinjiang Xu

и другие.

Medicine, Год журнала: 2024, Номер 103(19), С. e37998 - e37998

Опубликована: Май 10, 2024

Hepatocellular carcinoma (HCC) is one of the most common cancers globally, seriously endangering people health. Vitamin D was significantly associated with tumor progression and patients’ prognosis. Integrative 10 machine learning algorithms were used to develop a D-related signature (VRS) training cohort 3 testing cohorts. The performance VRS in predicting immunology response verified using several approaches. optimal constructed by stepCox + superPC algorithm. acted as risk factor for HCC patients. patients high-risk score had poor clinical outcome AUCs 1-, 3-, 5-year ROC 0.786, 0.755, respectively. A higher level CD8 cytotoxic T cells B obtained low-risk score. There PD1&CTLA4 immunophenoscore TMB Lower TIDE escape found cases IC50 value camptothecin, docetaxel, crizotinib, dasatinib, erlotinib lower cancer-related hallmarks, including angiogenesis, glycolysis, NOTCH signaling. Our study proposed novel HCC, which served an indicator immunotherapy responses HCC.

Язык: Английский

Процитировано

2

A comprehensive investigation of PRMT5 in the prognosis and ion channel features of lung cancer DOI Creative Commons
Yan Wang,

Daifang Chu,

Haichao Li

и другие.

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Ноя. 29, 2024

The increasing incidence and mortality associated with lung cancer (LC) is a significant global health challenge. underlying mechanisms contributing to LC remain inadequately understood. However, emerging evidence suggests that the epigenetic modifier protein arginine methyltransferase 5 (PRMT5) plays complex role in various cellular processes, including DNA repair, gene transcription, alternative splicing, through its function catalyzing symmetric dimethylation of both histone non-histone proteins. In this study, we examined functional PRMT5 utilizing LC-related datasets (GSE30219, GSE50081, TCGA cohort) series analyses. Our findings revealed was significantly overexpressed samples compared normal tissues correlated overall survival disease-free rates. Additionally, PRDM1 identified as key exhibiting strong interaction PRMT5. prognostic model integrated clinical factors demonstrated robust performance assessing outcomes. Elevated levels were poor prognosis LC, evidenced by analyses GSE30219, TCGA-LC datasets. Furthermore, 27 ion channel (IC) genes exhibited correlation adenocarcinoma (LUAD), which 9 statistically KM analysis. Strikingly, all genes, LRRC8A, same PRMT5, LUAD. research highlights potential novel biomarker relationship IC LC.

Язык: Английский

Процитировано

0

The Druggable Target Potential of NF-κB-Inducing Kinase (NIK) in Cancer DOI Creative Commons
Yina Wang, Liangyou Rui

International Journal of Translational Medicine, Год журнала: 2024, Номер 5(1), С. 1 - 1

Опубликована: Дек. 25, 2024

NF-κB-inducing kinase (NIK) is primarily recognized for its role as the apical that activates non-canonical NF-κB signaling and involvement in immune system regulation. NIK crucial maintaining cellular health by regulating fundamental processes such differentiation, growth, survival. Emerging evidence suggests dysregulated expression or function of non-lymphoid cells a key factor cancer progression. While deficiency causes severe dysfunction, overexpression excessive activation linked to inflammatory diseases, metabolic disorders, development. The development small molecule inhibitors targeting has sparked optimism clinical intervention, positioning promising druggable mediator cancer. ongoing progress creating novel offers new opportunities testing NIK-targeted therapies, potentially advancing application NIK-based treatments.

Язык: Английский

Процитировано

0