Ask about this productRelated genes to: CHK1 protein
- Gene:
- CHEK1 NIH gene
- Name:
- checkpoint kinase 1
- Previous symbol:
- -
- Synonyms:
- CHK1
- Chromosome:
- 11q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-04-21
- Date modifiied:
- 2011-11-11
Related products to: CHK1 protein
Related articles to: CHK1 protein
- Neuroendocrine neoplasms (NENs) are a biologically heterogeneous group of epithelial malignancies arising from neuroendocrine cells across multiple organs. Although considered rare in comparison to other solid tumors, their incidence has increased more than six-fold in recent decades. A major clinical challenge is the accurate stratification between aggressive, poorly differentiated (PD) neuroendocrine carcinomas (NECs) and slow growing well-differentiated (WD) neuroendocrine tumors (NETs), which differ significantly in prognostic outcomes and treatment response. Conventional histopathology is often insufficient for reliable classification or determination of tumor origin, motivating the need for molecularly informed diagnostic approaches. - Source: PubMed
Publication date: 2026/09/15
Khumpan TimothyChewe KasondeVijayvergia NamrataEleam EricQuiñones-Romero Juan NicolasPeri SurajYulan GongEngstrom Paul FCai Kathy QPei JianmingAlekbaeva Gulnaz DCampbell Kerry SWhetstine Johnathan RAstsaturov IgorLee Hayan - Tarin exhibits immunomodulatory and antiproliferative properties against several tumor cell lines. Nano-encapsulation in liposomes enhances its therapeutic potential by improving protein stability, bioavailability, and sustained release. Previous studies demonstrated that nano-encapsulated tarin induces cell cycle arrest, migration inhibition, apoptosis, and autophagy in triple-negative breast cancer cells; however, the molecular mechanisms underlying these effects remain poorly understood. To investigate the proteomic response elicited by nano-encapsulated tarin, MDA-MB-231 cells were treated for 24 and 48 h. Intracellular proteins were extracted, digested with trypsin, and analyzed by label-free LC-2D-MS/MS using HDMSE acquisition. Differentially expressed proteins were identified and quantified using the Progenesis QI platform, and then functional classification and pathway enrichment analyses were performed. A total of 2818 proteins were identified, of which 2150 displayed time-dependent modulation following treatment. After 24 h, cells exhibited an adaptive stress response profile characterized by increased DNA repair proteins (, ), migration/remodeling factors (, , ), and immune/cell cycle regulators (, ), while antioxidant proteins (, ) and BRCA1 were reduced, indicating oxidative stress and DNA damage. After 48 h, the proteomic profile shifted toward cell death, with increased , , , and CASP8 expression, disruption of DNA repair and cell cycle regulators (, , , ), and decreased migration-related proteins (, , , ). Nano-encapsulated tarin promotes a time-dependent transition from early adaptive stress responses to apoptosis, autophagy, cell cycle disruption, and loss of migratory capacity. These findings provide novel insights into the molecular mechanisms underlying tarin antitumoral activity and support its potential as a promising therapeutic strategy against triple-negative breast cancer. - Source: PubMed
Publication date: 2026/09/07
Cardoso Raiane VPereira Patricia RFreitas Cyntia SSouza Yuri PKalume Dário EVerissimo da Costa Giovani CarloConte-Junior Carlos APaschoalin Vania Margaret Flosi - To investigate the causal relationship between type 2 diabetes mellitus (T2DM) and fracture and identify molecular targets linking T2DM to impaired osteogenesis, we performed two-sample Mendelian randomization (MR) using large-scale GWAS data, followed by integrated bioinformatic and machine learning analyses of T2DM-, fracture-, and osteoblast differentiation-related datasets. Hub genes were identified through WGCNA, differential expression analysis, PPI network analysis, and multiple machine learning algorithms, and further evaluated by GSEA, cross-dataset validation, and immune cell infiltration analysis. In vitro validation was performed in MC3T3-E1 preosteoblasts cultured under normal-glucose, high-glucose, and osmotic-control conditions using Alizarin Red S staining, qRT-PCR, and Western blotting. MR analysis confirmed a positive causal effect of T2DM on fracture risk without evidence of horizontal pleiotropy. A total of 280 overlapping genes were identified, mainly enriched in extracellular matrix organization, ossification, bone remodeling, osteogenic differentiation, and pathways related to the cell cycle and AGE-RAGE signaling. PLK1, CCNA2, and CHEK1 were identified as hub genes and were associated with cell cycle regulation. Cross-dataset validation confirmed their upregulation in T2DM patients, while immune infiltration analysis indicated a predominance of neutrophils. High-glucose exposure markedly impaired osteogenic mineralization in MC3T3-E1 cells and dysregulated PLK1, CCNA2, and CHEK1 expression at both the mRNA and protein levels. Collectively, T2DM may increase fracture risk and impair bone regeneration through dysregulated cell cycle and AGE-RAGE signaling, with PLK1, CCNA2, and CHEK1 representing potential therapeutic targets. - Source: PubMed
Publication date: 2026/09/24
Sun ShulongChen QianLi HuaCao YujingLi Ji - Lung cancer remains a leading cause of cancer-related mortality worldwide, necessitating the development of novel therapeutic strategies. Matrine, a natural alkaloid derived from Sophora flavescens, has demonstrated broad antitumor properties, yet its underlying mechanisms, particularly concerning DNA damage response, remain incompletely elucidated. This study integrates network pharmacology, bioinformatics, and experimental validation to uncover a novel dual-targeting mechanism of matrine in lung cancer. Bioinformatics analysis identified CHEK1 as a key potential target. In vitro, matrine selectively inhibited proliferation, migration, invasion, and clonogenic survival of A549 and LLC cells, while reducing the G2/M phase proportion, indicating G2/M checkpoint impairment. Mechanistically, matrine concurrently downregulated CHEK1, p-PI3K, p-AKT, BCL-2, and EMT markers (Vimentin, MMP2, MMP9), and upregulated γH2AX, E-cadherin, Bax, and Cleaved Caspase-3. Crucially, siRNA experiments revealed that PI3K knockdown induced apoptosis without affecting CHEK1/γH2AX, whereas CHEK1 silencing promoted apoptosis independently of PI3K/AKT, demonstrating complementary. In vivo, matrine significantly inhibited LLC tumor growth in a xenograft model, suppressed proliferation (Ki67), and modulated the CHEK1-PI3K/AKT axis, corroborated by IHC and Western blotting. Importantly, matrine exhibited no significant systemic toxicity. Our findings unveil that matrine exerts potent antitumor effects by simultaneously inhibiting CHEK1-mediated DNA repair and PI3K/AKT survival signaling, presenting a novel dual-targeting approach for lung cancer treatment. - Source: PubMed
Yu JianghaoChen SiyangHou TingtingWeng XianwuLiu YakunHuang JunchaoYang ZeshanBao JinyuZhou ChangshuaiLv WanqingWu QingzheXu YunZhou Jinshan - Glioblastoma (GBM) is the most malignant and prevalent primary brain tumor in adults, accounting for up to 60% of all adult brain tumor, classified as WHO grade 4. Uncontrolled cell-cycle progression is one of the hallmarks of GBM. The patient prognosis is still poor after multimodal treatment, underscoring the need for new therapeutic strategies. Derived from Piper cubeba, hinokinin is a bioactive dibenzylbutyrolactone lignan that has demonstrated interesting anticancer effects. However, little is known about its molecular processes in GBM. - Source: PubMed
Publication date: 2026/06/17
Anass OukhdouchYoussef NadirEl Mostafa SalmanKhalid JebhiBasma ZinbiSouad SellamiHanane Rais