MSH6 antibody Host Rabbit
- Known as:
- MSH6 (anti-) Host Rabbit
- Catalog number:
- 'GTX111661
- Product Quantity:
- 0.1 ml
- Category:
- -
- Supplier:
- ACR
- Gene target:
- MSH6 antibody Host Rabbit
Related genes to: MSH6 antibody Host Rabbit
- Gene:
- MSH6 NIH gene
- Name:
- mutS homolog 6
- Previous symbol:
- GTBP
- Synonyms:
- -
- Chromosome:
- 2p16.3
- Locus Type:
- gene with protein product
- Date approved:
- 1995-08-29
- Date modifiied:
- 2019-04-23
Related products to: MSH6 antibody Host Rabbit
Related articles to: MSH6 antibody Host Rabbit
- Ovarian cancer remains a leading cause of gynecologic cancer-related deaths worldwide. Deficiencies in BRCA1/2 are well-established biomarkers that predict sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). However, emerging evidence indicates that a subset of BRCA-proficient tumors also responds to PARPi therapy, suggesting the presence of additional molecular mechanisms. We hypothesized that the composition of the PARP1 protein complex and PARylation-mediated signaling contribute to PARPi response in BRCA-proficient HGSOC. We assessed PARPi response across a panel of BRCA-proficient ovarian cancer cell lines and identified distinct sensitive and resistant groups. Chemical proteomics with rucaparib revealed different PARP1 complexes including higher enrichment of MSH6 in sensitive cells. Co-immunoprecipitation analyses further confirmed differential assembly of PARP1-MSH6-PARP2 complexes between sensitive and resistant models. To explore PARylation signaling, we performed ADP-ribosylation proteomics using clickable NAD⁺ analogs, revealing distinct PARylation profiles between sensitive and resistant cell lines. CHAF1A, a known MSH6 interactor and PARP1 substrate, showed more pronounced reduction in ADP-ribosylation in PARPi-sensitive cells. Targeting MSH6 using CRISPR or siRNA decreased PARPi sensitivity. In addition, mTOR signaling was reduced in sensitive, but increased in resistant cells, following rucaparib treatment. Notably, MSH6 knockdown led to increased CHAF1A expression regardless of rucaparib treatment. Importantly, knockdown of CHAF1A significantly impaired cell viability, especially in A2780 cells, and suppressed mTOR signaling, suggesting that CHAF1A acts downstream of MSH6 to regulate the mTOR axis. Furthermore, co-treatment with mTORC1 inhibitors enhanced the cellular effects of rucaparib in resistant cells, suggesting a therapeutic potential of targeting downstream mTOR effectors to overcome intrinsic resistance. In conclusion, this study identifies the PARP1-MSH6 interaction to modulate PARPi sensitivity via CHAF1A-mTOR signaling in BRCA-proficient ovarian cancer. By integrating chemical proteomics and ADP-ribosylation proteomics, we delineate the interplay between PARP1 complex composition and signaling dynamics, highlighting MSH6 as a critical modulator of PARPi response and potential biomarker to enhance therapeutic efficacy in BRCA-proficient HGSOC. - Source: PubMed
Publication date: 2026/09/02
Deng OuNepomuceno Thales Da CostaFang BinWelsh Eric AIzumi VictoriaMartin Rachael HGeorge Erin MKoomen John MMonteiro Alvaro NRix Uwe - This case highlights the importance of genetic evaluation during treatment in young patients with advanced ovarian cancer. Lynch syndrome caused by a germline MSH6 pathogenic variant was diagnosed during first-line maintenance therapy, and pembrolizumab achieved a durable response in recurrent disease. - Source: PubMed
Publication date: 2026/08/31
Yokozawa TomomiNakagawa SayakoSuzuki YukioTokinaga-Uchiyama AyaKonnai KatsuyukiNarimatsu HirotoHiroshima YukihikoSaji Haruya - To create a non-invasive model for forecasting microsatellite instability (MSI) status in colorectal cancer (CRC) using preoperative F-FDG PET/CT metabolic parameters, guiding personalized treatment. - Source: PubMed
Publication date: 2026/08/31
Chen RDeng LWang JLin CGong Q - Genetic testing for Lynch and BRCA1/2-associated hereditary cancer syndromes is recommended in colon or pancreatic cancer patients, but their association with hepatocellular carcinoma (HCC) risk is unknown. We evaluated associations between rare germline variants in DNA-repair genes and HCC risk across ancestrally diverse cohorts. - Source: PubMed
Publication date: 2026/08/29
Garofalo Alexis MChotiprasidhi PerapaJohnson Josephine PrincySato-Espinoza KarinaMa JunMiller HunterO'Brien DanielGuare LindsayCardone Katie MPalmiero NicoleRodriguez ZacharyKaplan David ELynch Julie ATsao Philip SRader Daniel JRoberts Lewis RDebes Jose DOdeghe EmuoborLesi FunmilayoOyeleke GaniyatMattos Ângelo ZArrese MarcoCarrera EnriquePrieto JhonBoonstra AndreDiaz-Ferrer JavierOkeke Edith NWang JunHou LifangAgyei-Nkansah AdwoaAfihene Mary YeboahAwuku Yaw AsanteNyanga Albert Chang Kyong-MiAntwi Samuel OVujković MarijanaVerma AnuragWangensteen Kirk J - Lung cancer remains the leading cause of cancer-related mortality in the United States, characterized by poor overall survival rates (OS), particularly for advanced-stage disease. While smoking is a primary risk factor, other contributors include environmental exposures, genetics, comorbidities, and socioeconomic factors. We included 232 patients with lung cancer (96% NSCLC). Patients were categorized into DNA damage response (DDR)-mutant (DDR, = 67, 29%) and DDR-wild-type (DDR, n = 165, 71%) groups. We evaluated the correlations between individual and socioeconomic factors between DDR and DDR lung cancer patients. Nineteen DDR genes were identified, with 31.3%, 19.4%, 14.9%, 14.9%, 11.9%, 11.9%, 8.9%, and (5.9%) being the most common. The DDR group had a significantly higher median tumor mutational burden (TMB) (12 vs. 9; = 0.006) and a higher prevalence of adenocarcinoma (85.1% vs. 64.8%, = 0.003). Logistic regression identified adenocarcinoma histology (OR = 10.03, = 0.002) and lower area deprivation index (OR = 0.98, = 0.04) as predictors of DDR mutation status. Having advanced stage at diagnosis was associated with, age ( = 0.03), lack of lung cancer screening ( < 0.001), and adenocarcinoma histology ( < 0.001). While median OS was 61 months for the DDR group vs. 44 months for the DDR group ( = 0.654), patients with mutations had significantly shorter survival (13 vs. 67 months; = 0.0008). Population-level factors, including food insecurity (HR = 2.33, = 0.002), lack of insurance (HR = 2.39, = 0.008), and proximity to potential chemical accidents (HR = 1.73, = 0.037), were significant predictors of OS. These findings suggest that DDR lung cancers represent a biologically distinct subgroup characterized by higher tumor mutational burden and enrichment for adenocarcinoma histology; however, DDR mutation status alone was not associated with overall survival. Instead, outcomes appeared to vary by individual DDR gene, with alterations identifying a subgroup with particularly poor survival. In parallel, food insecurity, lack of insurance, and proximity to potential environmental hazards were associated with outcomes, highlighting the need to integrate genomic biomarkers with social and environmental determinants of health. These data suggest the need for future prospective studies incorporating treatment-response data, longitudinal social determinants of health (SDOH) assessment, and environmental exposure measures to define how DDR alterations can guide precision oncology strategies while addressing modifiable barriers to equitable cancer care. - Source: PubMed
Publication date: 2026/08/13
Nanaa AhmadKao JeremyDavis MartinPasquinelli MaryGeise Margaret WrightLiu LiNguyen Ryan Huu-TuanWeinberg Frank