ASS1 (Argininosuccinate synthase 1)

Particularly noteworthy is the downregulation of CYP51A1, which is known to confer TKI resistance under normal circumstances, and therefore directly associated with increased TKI sensitivity in BCR-ABL1 p190-positive cells. Another interesting feature is SPART, whose abundance was increased despite strong promoter hypermethylation, indicating that some transcriptional changes in BCR-ABL1 p190-carrying cells occur independently of promoter methylation and reflect broader regulatory effects of the fusion.

Mechanistic investigation revealed that 10f induces tumor cell apoptosis by modulating the AMPK/mTOR signaling pathway through ASS1 activation. In vivo studies confirmed that 10f possesses significantly improved antitriple-negative breast cancer efficacy compared to SPA, highlighting its substantial therapeutic potential.

Our study uncovers layer-specific molecular landscapes in tongue OLP and identifies KRT17 as a candidate implicated in immune-epithelial crosstalk, providing novel insights into pathogenesis and a potential direction for future therapeutic exploration.

Biological evaluation revealed a strong correlation between the antitumor effects of these compounds and their ability to activate ASS1. For optimal activity, the introduction of a suitable aminoalkyl side chain at the nitrogen atom of dimethyl-Spinosyn A proved to be essential.

Together, these findings reveal a TME-driven, targetable stromal-immune circuit that enables tumors to withstand arginine deficiency-induced metabolic stress. Broadly, our work highlights that mapping and strategically inducing metabolic dependencies can reveal actionable compensatory pathways, offering opportunities to improve cancer therapy.

A cancer-related fatigue model was established by orthotopic injection of 4T1 cells to induce breast cancer, combined with intraperitoneal injection of paclitaxel...The underlying mechanism may involve modulation of Arg biosynthesis and metabolic pathways to maintain systemic arginine homeostasis. These findings provide a preliminary foundation for elucidating the mechanism of Fufang E'jiao Jiang in managing breast cancer chemotherapy-related muscle fatigue.

Dysregulation of key enzymes such as GLS1, ASS1 and IDO1 further highlights potential therapeutic targets. Exploiting these vulnerabilities through metabolic inhibitors or rational combinations with targeted and immunotherapy holds promise for overcoming resistance and improving outcomes in ccRCC.

MK-2206 and rapamycin suppressed the expression of ASS1 in H446-BR cell. In xenograft model, BCT-100 has little anti-tumor effect on H446-BR compared with H446 as well as H446-BR silenced sestrin3. Collectively, these results elucidate SESN3 plays an essential role in resistant mechanism, which will provide a valuable source of information for translational research.

Notably, restoration of c-Myc effectively rescued T-ALL cells from the suppressive effects induced by ASS1 depletion. Collectively, our findings demonstrate that ASS1 supports mTORC1/c-Myc pathway activity by regulating arginine availability, thereby promoting the survival of T-ALL cells and leukemia progression.

EVO downregulates ASS1 via the Wnt/β-catenin/c-MYC pathway disrupts CRC arginine synthesis metabolism and inhibits CRC cell proliferation/migration. These results support the interaction between metabolic regulation and signaling pathways, highlighting EVO as a promising CRC therapeutic candidate.

Background/Objectives: Despite the introduction of targeted therapies such as Nivolumab, survival outcomes for patients with esophageal adenocarcinoma remain poor. This underscores the urgent need for clinical trials evaluating the efficacy of pegargiminase in this patient population. Additionally, incorporating ASS1 immunohistochemical staining into pre-neoadjuvant biopsy assessments should be considered to optimize neoadjuvant treatment strategies and advance the implementation of personalized cancer therapy.