Ask about this productRelated genes to: RICTOR antibody
- Gene:
- RICTOR NIH gene
- Name:
- RPTOR independent companion of MTOR complex 2
- Previous symbol:
- -
- Synonyms:
- MGC39830, AVO3, PIA, KIAA1999
- Chromosome:
- 5p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2009-05-29
- Date modifiied:
- 2019-03-19
Related products to: RICTOR antibody
Related articles to: RICTOR antibody
- Monocyte exhaustion is a dysfunctional immune state marked by persistent inflammation and immune suppression, reflected in STAT1-mediated expression of pathogenic inflammatory mediator CD38 and immune suppressive PD-L1, as well as a suppression of Akt signaling and a reduction of immune-enhancing mediator CD86. While prolonged Toll-like receptor 4 (TLR4) stimulation induces monocyte exhaustion, the roles of other TLRs remain unclear. Here, we systematically evaluated the ability of TLR-2, TLR-3, TLR-7, and TLR-9 agonists to induce murine bone marrow-derived monocytes exhaustion in vitro. Although all tested agonists promoted exhaustion phenotypes to varying degrees, characterized by upregulation of STAT1 mediated expression of CD38 and PD-L1, only TLR-2 and TLR7 agonists drastically suppressed Akt and CD86. In contrast, TLR-3 or TLR-9 agonists preferentially sustained Akt activation and CD86 expression. Mechanistically, STAT1/STAT3 activation mediated by mTROC1 was common across TLR agonists responsible for elevated expression of CD38 and PD-L1. On the other hand, Akt signaling mediated by mTORC2 responsible for the expression of CD86 was preferentially suppressed by TLR-2 and TLR-7 agonists, but retained by TLR-3 and TLR-9 agonists. Deletion of Rictor, a key component of mTORC2, blocked the activation of Akt/CD86 triggered by TLR-3/9 agonists, and further elevated mTORC1 mediated activation of STAT1/3 as well as CD38 expression. Conversely, Fumagillin or Rapamycin treatment, which has been associated with reduced mTORC1 signaling activity, mitigated TLR-2/7-induced STAT1/STAT3 activation and CD38 expression. These findings reveal that monocyte exhaustion is a shared but differentially regulated outcome of distinct TLR pathways, with the mTOR axis potentially serving as a key therapeutic target for immune dysfunction. - Source: PubMed
Publication date: 2026/05/20
Wang JingWu YajunLee GraceRazani BabakLi Liwu - A widening spectrum of renal tumors is driven by alterations in mTOR pathway genes. We examined the relationship between the specific underlying genomic driver mutation, mTOR signaling activation and tumor histologic subtype among mTOR pathway-altered tumors. mTOR pathway activation was assessed by quantifying expression of GPNMB in 16 cases of eosinophilic vacuolated tumor (EVT), 13 cases of low grade oncocytic tumor (LOT), 10 cases of eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and 1 case of xanthomatous giant cell renal cell carcinoma (XGC-RCC), all with previous sequencing. p-S6 expression was additionally quantified in the LOT and EVT cases. A literature review of 217 previously reported mTOR pathway-altered renal tumors identified the frequency of driver alterations by histologic subtype. GPNMB and p-S6 expression were correlated with one another (r=0.51, p=0.007) and GPNMB expression was higher among tumors with underlying TSC1/2 alterations compared to MTOR/PIK3CA alterations (p=0.02) with a nonsignificant trend for p-S6 (p=0.15). There was no significant association of GPNMB or pS6 with tumor histologic subtype in this series. In the literature, TSC1/2 alterations predominated in ESC-RCC (84%), though were less common in LOT (24%) where MTOR or other mTOR pathway mutations (PIK3CA, PTEN, RHEB, RICTOR, NF1/2) were frequent (55%). In EVT, RCC-FMS and renal hemangioblastoma, TSC1/2 and MTOR mutations occurred with similar frequency, with a slight predominance of the former. GPNMB expression is associated with p-S6 activation and is higher in renal tumors driven by TSC1/2 compared to MTOR/PIK3CA alterations, suggesting that it may be most useful in ESC-RCC. - Source: PubMed
Publication date: 2026/05/18
Bhardwaj SwatiAmaral AdriannaDairo OluwademiladeAkbari AmirPivovarcikova KristynaWilliamson Sean RAntic TatjanaArgani PedramAsrani KaushalLotan Tamara L - <b>Introduction:</b> Although genetic mutations have been reported in squamous cell carcinoma of unknown primary (SCCUP), no scientifically validated targeted therapies are currently available. Moreover, cancer genomic profiling tests remain underutilized in clinical practice. These issues highlight the urgent need to elucidate the genomic landscape of SCCUP and its potential therapeutic relevance.<b>Aim:</b> This study aimed to characterize the mutational profile of recurrent and/or metastatic SCCUP.<b>Materials and methods:</b> Data were analyzed for 170 consecutive patients with SCCUP registered at the Japan National Cancer Center, Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 2019 and August 2025. Genetic mutations were determined by next-generation sequencing. The survival of patients was determined by the log-rank test and a Cox proportional hazards model.<b>Results:</b> The top 10 mutations in SCCUP were <i>TP53</i> (57.6%), <i>CDKN2A</i> (37.0%), <i>PIK3CA</i> (32.9%), <i>KMT2D</i> (27.6%), <i>CDKN2B</i> (20.6%), <i>NOTCH3</i> (20.6%), <i>BRAC2</i> (20.0%), <i>PTEN</i> (16.5%), <i>NOTCH1</i> (15.9%), and <i>RICTOR</i> (15.9%), with 20.2 10.1 (mean SEM) mutations/ individual. Mutation in <i>BRCA2</i> (p = 0.0347) was associated with a significantly worse prognosis, as determined by the log-rank test. The hazard ratios for cases with this mutation was 2.3450 (95% CI, 1.2220-4.499, p = 0.01037) for <i>BRCA2</i>.<b>Conclusions:</b> This study delineated the mutational spectrum of recurrent and/or metastatic SCCUP. Even in advanced disease, prognostically relevant mutations were identified, emphasizing the clinical importance of cancer genomic profiling tests. - Source: PubMed
Nagano HiromiKiyama SatoshiKyutoku TakayukiMatsumoto HayatoYamashita Masaru - - Source: PubMed
Publication date: 2026/05/13
Lai PinlingSong QianchengYang ChengLi ZhenLiu SichiLiu BinLi MangmangDeng HongwenCai DaozhangJin DadiLiu AnlingBai Xiaochun - RICTOR, a scaffold protein of the mTORC2 complex, regulates AKT signaling and has been implicated in tumor progression and therapy resistance across multiple cancers. However, the prognostic impact of RICTOR mutations in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma remains unclear. This study aimed to evaluate the clinicopathological, molecular, and survival characteristics of patients with metastatic EGFR-mutant lung adenocarcinoma according to RICTOR mutation status. We retrospectively analyzed 235 patients diagnosed with de novo metastatic lung adenocarcinoma between 2018 and 2024 across three tertiary oncology centers. Patients with targetable oncogenic drivers other than EGFR (ALK, ROS1, HER2, KRAS G12C, BRAF V600E, RET, MET) were excluded. Next-generation sequencing (NGS) was performed using a hybrid-capture panel (Illumina TSO500). Clinical features, co-mutations, treatment responses, and overall survival (OS) were compared between RICTOR-mutant and wild-type subgroups within the EGFR-mutant cohort. Survival analyses employed Kaplan-Meier estimates, log-rank tests, and Cox regression modeling. Of the total cohort, 39 patients (17%) had EGFR-mutant tumors, of whom 15 (38%) carried RICTOR mutations. RICTOR-mutant cases were more likely to be former smokers and presented more frequently with bone and pleural metastases compared with wild type. Treatment patterns and RECIST v1.1 response rates did not significantly differ between groups. Median OS was significantly shorter in RICTOR-mutant versus RICTOR-wild patients (8 vs. 14 months, log-rank p < 0.001). In univariate analysis, RICTOR mutations were associated with inferior OS (HR 2.48, 95% CI 1.73-7.95, p = 0.03), and this association remained significant in multivariate analysis (HR 2.34, 95% CI 1.69-6.75, p = 0.021). Exploratory analyses suggested that RICTOR co-mutations with EGFR exon 19 deletions, exon 18 alterations, or exon 20 alterations were associated with poorer survival outcomes. RICTOR mutations were associated with a high-risk subset of EGFR-mutant metastatic lung adenocarcinoma characterized by more aggressive clinical features and worse survival. These findings suggest the need for prospective validation and support the potential integration of RICTOR status into molecular risk stratification frameworks for precision oncology. - Source: PubMed
Publication date: 2026/05/04
Aytac AliOzata Berkay MehmetErdogdu Ibrahim HalilAlkan AliTanriverdi Ozgur