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FOXD3 Is Functionally Linked to NF-ΞΊB Signaling in KRAS G12C-Mutant NSCLC Cells

Cells. 2026 Aug 28;15(17):1564. doi: 10.3390/cells15171564.

ABSTRACT

KRAS G12C mutation is a clinically relevant driver in non-small cell lung cancer (NSCLC), yet the signaling networks that modulate malignant behavior in this context remain incompletely defined. In this study, we examined the functional role of FOXD3 and its relationship with NF-ΞΊB signaling in KRAS G12C-mutant NSCLC models. Stable FOXD3 overexpression was established in SW1573 and LU65 cells. FOXD3 reduced cell viability, migration, and invasion while increasing caspase 3/7 activity in both cell lines. Transcriptomic profiling in LU65 cells followed by Hallmark enrichment analysis identified TNFΞ± signaling via NF-ΞΊB as a prominently altered pathway associated with FOXD3 overexpression. Consistently, NF-ΞΊB dual-luciferase assays showed reduced basal NF-ΞΊB transcriptional activity in FOXD3-overexpressing cells. TNFΞ± stimulation partially reversed the inhibitory effects of FOXD3 on proliferation, migration, and invasion and attenuated FOXD3-induced apoptosis. In addition, stable FOXD3 overexpression suppressed xenograft growth in vivo. Collectively, these findings support a functional association between FOXD3 overexpression and reduced NF-ΞΊB-related transcriptional activity in KRAS G12C-mutant NSCLC models, although the present data do not establish direct causal mediation by NF-ΞΊB.

PMID:42738858 | PMC:PMC13564895 | DOI:10.3390/cells15171564

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M$^3$-ACE: Rectifying Visual Perception in Multimodal Math Reasoning via Multi-Agentic Context Engineering

arXiv:2603.08369v1 Announce Type: new Abstract: Multimodal large language models have recently shown promising progress in visual mathematical reasoning. However, their performance is often limited by a critical yet underexplored bottleneck: inaccurate visual perception. Through systematic analysis, we find that the most failures originate from incorrect or incomplete visual evidence extraction rather than deficiencies in reasoning capability. Moreover, models tend to remain overly confident in their initial perceptions, making standard strategies such as prompt engineering, multi-round self-reflection, or posterior guidance insufficient to reliably correct errors. To address this limitation, we propose M3-ACE, a multi-agentic context engineering framework designed to rectify visual perception in multimodal math reasoning. Instead of directly aggregating final answers, our approach decouples perception and reasoning by dynamically maintaining a shared context centered on visual evidence lists. Multiple agents collaboratively contribute complementary observations, enabling the system to expose inconsistencies and recover missing perceptual information. To support stable multi-turn collaboration, we further introduce two lightweight tools: a Summary Tool that organizes evidence from different agents into consistent, complementary, and conflicting components, and a Refine Tool that filters unreliable samples and guides iterative correction. Extensive experiments demonstrate that M3-ACE substantially improves visual mathematical reasoning performance across multiple benchmarks. Our method establishes new state-of-the-art results 89.1 on the MathVision benchmark and achieves consistent improvements on other related datasets, including MathVista and MathVerse. These results highlight the importance of perception-centric multi-agent collaboration for advancing multimodal reasoning systems.
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