Daxx
- Known as:
- Daxx
- Catalog number:
- 11-351-C025
- Product Quantity:
- 0.025 mg
- Category:
- -
- Supplier:
- Exbio
- Gene target:
- Daxx
Related genes to: Daxx
- Gene:
- DAXX NIH gene
- Name:
- death domain associated protein
- Previous symbol:
- -
- Synonyms:
- DAP6
- Chromosome:
- 6p21.32
- Locus Type:
- gene with protein product
- Date approved:
- 1998-03-25
- Date modifiied:
- 2016-10-05
Related products to: Daxx
Related articles to: Daxx
- Neuroendocrine neoplasms (NENs) represent a heterogeneous group of malignancies ranging from relatively indolent well-differentiated neuroendocrine tumors (NETs) to more aggressive poorly differentiated neuroendocrine carcinomas (NECs). The advent of somatostatin receptor (SSTR)-targeting therapies, particularly radioligand therapy (RLT), has transformed the therapeutic landscape of NETs. Ongoing efforts are aimed at maximizing the therapeutic benefit of RLT and include retreatment and combination strategies as well as novel α-emitter-based radiopharmaceuticals. The increasing use of molecular profiling has led to the identification of recurrent canonical alterations in pancreatic NETs, including in , /, PI3K/Akt/mTOR, and angiogenic signaling pathways, facilitating the development of effective targeted therapies. However, despite the addition of newer targeted therapies to the therapeutic armamentarium, resistance remains inevitable and highlights the need for improved predictive markers to inform therapy sequencing and novel biomarker-selected therapies. In addition, the development of novel therapeutic strategies including SSTR antagonists, nonpeptide drug conjugates, and novel radiopharmaceutical constructs highlights the potential of biomarker-informed therapies in this space. By contrast, treatment options for NECs remain limited, with modest therapeutic benefit of platinum-based chemotherapy. The identification of delta-like ligand 3 (DLL3) as a therapeutic target in high-grade NENs has led to the development of novel targeted therapies such as T-cell engagers, which have demonstrated promising activity in early phase clinical trials. In addition, other DLL3-targeting agents such as antibody-drug conjugates, trispecific engagers, and cellular therapies remain under investigation. Collectively, these advances underscore the potential of biomarker-informed treatment approaches to personalize treatment decisions and improve long-term outcomes across the NEN spectrum. - Source: PubMed
Publication date: 2026/06/26
Grewal Udhayvir SShaheen ShaguftaZhen David BMittra Erik SHalfdanarson Thorvardur RSingh SimronChan Jennifer A - Neuroendocrine carcinomas of the gallbladder (GBNECs) have been very poorly characterized. In this study, 31 NECs were identified through an analysis of 636 GB cancers and contrasted with the ordinary GBCs (O-GBCs) in the same cohort. Seven were pure small cell NECs, 2 pure large cell, and 22 had mixed adenocarcinoma component (with NEC component being small cell in 6 and large cell in 16). High-grade glandular dysplasia was evident in 15 (6 as intracholecystic neoplasms; vs. 6% in O-GBC), F:M ratio was 5.2:1, and median age was 58 (vs. 65 in O-GBC). The average neuroendocrine component constituted 80% of the tumor; the median Ki-67 was 70%; lymph-vascular invasion was seen in 74%, and perineural invasion in 56%. GBNECs presented with more advanced tumors; 72% were pT3/T4 (vs. 26% in O-GBC, P=0.001). Lymph node metastasis was in 5/10 (with lymph nodes available in the specimen), and 5 had distant metastases. Tumor cells were positive for neuroendocrine markers (synaptophysin 95%, chromogranin 75%, CD56 90%), keratins (AE1/3 90%, Cam5.2 88%), with upper-GI profile (CK7 65%; CK20 0%); TTF-1 in 25%. pRB loss was detected in 67%, positive p16 83%, mutant p53 88.8%, and SMAD4 loss in 24%. Overall, the pRB/p16 pathway was inactivated in 83% (12 [67%] as pRB loss/p16+, and 3 [17%] as pRB+/p16- ). DAXX was retained in all. Loss of pRB and p16 was also detected in about a third of the adenocarcinoma and preinvasive components. ATRX loss was noted in 1 large-cell NEC. The median survival was 6.1 months, significantly shorter than O-GBCs, although a few survived unexpectedly longer. Factors associated with shorter survival included pT3 versus pT2 stage, and a trend for lower synaptophysin and CD56 expression. In conclusion, NECs constitute <5% of GBCs, and two-thirds are admixed with an adenocarcinoma component. A fifth arises in intracholecystic neoplasms. Inactivation of the pRB/p16 pathway is common, with 2/3 showing pRB loss. They present as advanced tumors and behave aggressively. - Source: PubMed
Publication date: 2026/06/24
Reid Michelle DPehlivanoglu BurcinMemis BaharRoa Juan CMuraki TakashiKoshiol JillLicitra GiancarloGoodman MichaelAraya Juan CVillaseca MiguelLosada HectorSarmiento Juan MDursun NevraBasturk OlcaAdsay Volkan - The alternative lengthening of telomeres (ALT) pathway is a telomerase-independent telomere maintenance mechanism, which is frequently observed in osteosarcoma. In this study, we performed a systematic review of studies assessing ALT in patient-derived osteosarcoma samples using direct experimental assays, alongside bioinformatic analysis of large public genomic datasets to evaluate the prevalence of canonical ALT-associated alterations. Across seven eligible studies comprising 342 tumours, ALT activity was identified in 62.9% of cases. In contrast, analysis of the Target-OS and PeCan datasets demonstrated that mutations in ATRX or DAXX, and amplification of TOP3A, occur at substantially lower frequencies, collectively accounting for only a minority of tumours. Statistical comparison confirmed a significant discrepancy between experimentally-observed ALT prevalence and the frequency of these canonical ALT-associated genetic alterations. These findings indicate that canonical genomic events are insufficient to explain ALT activation in osteosarcoma and support a model of marked biological heterogeneity. Potential alternative mechanisms include non-mutational disruption of chromatin remodelling pathways, replication stress-associated processes, and epigenetic dysregulation. The data highlights the limitations of relying on sequencing-based approaches alone to infer telomere maintenance mechanisms, which could have important clinical consequences for potential ALT-pathway targeting therapies. In conclusion, ALT is highly prevalent in osteosarcoma but is not adequately captured by known genetic correlates. Functional assays remain essential for accurate classification, and improved understanding of non-canonical ALT drivers will be critical for biomarker development and the design of targeted therapeutic strategies. - Source: PubMed
Publication date: 2026/06/02
Goncalves TomasMattis Natalie SMitchell Amy F MRose Anna M - Valosin-containing protein (VCP), a conserved AAA ATPase hexamer, participates in multiple biological processes including ERAD, ubiquitin-dependent degradation by extracting misfolded proteins for proteasomal degradation. Although its interactions with cofactors are well-characterized, and its dysregulation is implicated in multisystem proteinopathy, amyotrophic lateral sclerosis, and cancer, the tissue-specific VCP interactomes underlying its functional versatility remain elusive. Here, we generated HA-N-tagged VCP knock-in mice via CRISPR/Cas9 strategy and performed affinity purification coupled with data-independent acquisition (DIA) mass spectrometry to systematically profile VCP interactors across eight mouse tissues, yielding a high-confidence dataset. We identified 923 robust VCP-binding partners, including established interactors (UBX2B, UFD1, proteasomal subunits) and novel candidates implicated in energy metabolism (TCA cycle, oxidative phosphorylation) and protein quality control (proteasome, ERAD). Notably, we validated the interaction of VCP to two hepatic candidate proteins, DAXX and PRKAG2 (AMPK γ2 regulatory subunit), using HepG2 cells. This study establishes the first in vivo atlas of the VCP interaction network, providing mechanistic insights into its tissue-specific roles and highlighting potential therapeutic avenues for VCP-related disorders. - Source: PubMed
Publication date: 2026/06/13
Wang NannanLi YiningLi NaShen LinruWang ChengzhiZhu HuimingZhou ZiyueDing YibingZhang JingziFang LeiBai Bing - Corticotroph adenomas include functioning tumors causing Cushing disease (CD) and silent corticotroph adenomas (SCA), which differ markedly in size, clinical presentation, and aggressiveness. The molecular basis for these differences remains incompletely understood. - Source: PubMed
Publication date: 2026/06/11
Paes TicianaZhang QilinBorges Clarice OrangeMohan Dipika RVaz VictorSoares Beatriz SantanaCarroll Rona SKaiser Ursula BSmith Timothy RBi Wenya LindaMeredith DavidLerario Antonio MAbreu Ana Paula