RRAGD (Ras related GTP binding)

Conversely, pharmacological inhibition of mTORC1 or genetic ablation of Irtks ameliorates hepatic steatosis, inflammation, and metabolic dysfunction in mouse models. Our study establishes IRTKS as a central regulator of mTORC1-dependent metabolic reprogramming during hepatocarcinogenesis, providing potential therapeutic targets for MASLD-associated liver cancer.

Additionally, cell proliferation was inhibited, and profiling of gene and protein expression indicated a downregulation of several other components of the mTOR pathway, suggesting a broad inhibitory effect of miR-302/367 on mTOR signaling. These results reveal a novel molecular mechanism by which the miR-302/367 cluster may exert tumor-suppressive effects by modulating mTOR pathway activity at multiple levels in breast cancer cells, thereby suggesting its potential relevance for future therapeutic investigation in cancer treatment.

Additionally, PSAT1 knockout caused a compensatory upregulation of the serine transporter solute carrier family 1 member 5 (SLC1A5), increasing exogenous serine uptake. In conclusion, our study reveals a novel function of PSAT1 in regulation of mTORC1 that affects the proliferation of LUAD cells.Abbreviations: ATG5: autophagy-related 5; BECN1: Beclin 1; CQ: chloroquine; 4EBP1: eukaryotic translation initiation factor 4E binding protein 1; GAP: GTPase-activating protein; GDP: Guanosine nucleotide diphosphate; GTP: Guanosine triphosphate; GTPase: guanosine triphosphatase; LAMP2: lysosome-associated membrane protein 2; LC3: microtubule-associated protein 1 light chain-3, LUAD: lung adenocarcinoma; mTORC1: mechanistic target of rapamycin complex 1; PCC: Pearson's correlation coefficient; PSAT1: Phosphoserine aminotransferase 1; Rag: Ras-related GTP binding; Raptor: regulatory-associated protein of mTOR; S6: ribosomal protein S6; S6K1: substrates S6 kinase 1; SLC1A5: solute carrier family 1 member 5; SSP: serine biosynthetic pathway; ULK1: unc-51 like autophagy activating kinase 1.

Mechanistically, LINC00622 associates with and recruits BTF3 to transcriptionally enhance RRAGD expression for activating mTORC1 and thus inhibiting autophagic cell death, which contributes to the development of cutaneous melanoma. Our findings not only demonstrated the oncogenic role of LINC00622 via RRAGD/mTORC1 axis to repress autophagic cell death in cutaneous melanoma, but also offer novel treatment targets for melanoma therapy.

DHA inhibited tongue-to-lymph node metastasis through RALB, providing a novel therapeutic strategy for TSCC metastasis.

Moreover, a significant disparity in drug sensitivity to AZD8055, paclitaxel, and PD0325901 was noted between the high-risk and low-risk cohorts, and the established four-gene risk signature served as dependable prognostic indicators in the validation cohort, confirmed at the cellular level through external dataset validation and reverse transcription quantitative PCR (RT-qPCR) experiments. A risk signature based on GRGs was established for OS, exhibiting robust predictive efficacy for prognostic assessment, and offering significant clinical utility for the prognosis of OS.

RalB act as a prognostic gene in HNSCC, and promote lymph node metastasis in early stage of TSCC.

We show that IL4 treatment induced RRAGD expression, that RRAGD is required for mTOR activation in lymphoma cells and that IL4-enhanced BCR signaling induced mTOR activation. The IL4 and BCR-induced mTOR activation was reduced by CREBBP mutants and augmented by mutant STAT6, establishing a link between STAT6 mutations and mTOR regulated pro-growth pathways in lymphoma.

We summarize the regulatory processes governing the expression of Rab22a and the mutants of Rab22a. Notably, the present understanding of complex interactions between Rab22a and EVs are highlighted, encompassing both the impact of Rab22a on the genesis of EVs and the role of EVs that are affected by Rab22a mutants in propelling tumor advancement. The dynamic interaction between Rab22a and EVs plays a significant role in the progression of tumors, and it can provide novel insights into the pathogenesis of cancers and the development of new therapeutic targets.

Of these, all pts received a platinum-based 1L CT, mainly carboplatin in combination with paclitaxel...For 87 pts (38%) a maintenance therapy after 1L CT was already documented: 44 pts were treated with bevacizumab, 23 pts with niraparib, 6 pts with olaparib and 14 pts with the combination of olaparib and bevacizumab... The prospective cohort study SMARAGD for the first time presents real-world data on the use of 1L maintenance therapy in pts with newly diagnosed aOC. Two thirds of pts who have completed 1L CT for aOC have received maintenance therapy so far. Future analysis will reveal the use of maintenance therapy depending on the biomarker status and the outcome of 1L maintenance therapy in real-world.

Depletion of both MEF2A and MEF2D or expressing the unphosphorylatable MEF2D mutant suppressed tumor cell growth. Thus, our study revealed a transcriptional regulatory mechanism of MTORC1 that promoted cell anabolism and proliferation and uncovered its critical role in pancreatic cancer progression.Abbreviation: ACTB: actin beta; ChIP: chromatin immunoprecipitation; EGF: epidermal growth factor; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; FLCN: folliculin; FNIP1: folliculin interacting protein 1; FNIP2: folliculin interacting protein 2; GAP: GTPase activator protein; GEF: guanine nucleotide exchange factors; GTPase: guanosine triphosphatase; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MEF2: myocyte enhancer factor 2; MEF2A: myocyte enhancer factor 2A; MEF2D: myocyte enhancer factor 2D; MEF2D-3YF: Y131F, Y333F, Y337F mutant; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; NR4A1: nuclear receptor subfamily 4 group A member 1; RPTOR: regulatory associated protein of MTOR complex 1; RHEB: Ras homolog, mTORC1 binding; RPS6KB1: ribosomal protein S6 kinase B1; RRAG: Ras related GTP binding; RT-qPCR: real time-quantitative PCR; SRC: SRC proto-oncogene, non-receptor tyrosine kinase; TMEM192: transmembrane protein 192; WT: wild-type.

Animal studies confirmed that RRAGB over-expression obviously inhibits the tumor growth both in the xenograft and orthotopic mouse glioma models, along with improved overall survival rates. In short, we provide evidence that RRAGB is a potential therapeutic target and prognostic marker for GBM treatment.