FOSL1 (FOS Like 1)

Our study defines a FOSL1-TCOF1-ribosome axis that promotes CPT tolerance in NSCLC by maintaining HR repair. These findings provide a rationale for targeting ribosome biogenesis to enhance CPT-based treatment and highlight coordinated regulation of transcription, protein synthesis, and DNA repair under chemotherapeutic stress.

Furthermore, our findings show that the dual-targeting agents JQ-1 and CX-6258-focused on FOSL1/AP-1 and PIM kinases, respectively-effectively suppress both the progenitor properties and the growth of mouse and human DNPC surrogates in vitro and in vivo. Thus, early eradication of castration-tolerant Club-like cells presents a promising therapeutic strategy to mitigate prostate cancer progression toward CRPC.

From a therapeutic standpoint, targeting the FOSL1/IKKα/UCHL3 feedback axis yielded significant attenuation of multiple malignant phenotypes of GBM using a novel nanoparticle-based siRNA delivery system (plofsome@siFOSL1), which effectively suppressed FOSL1 expression. The findings of this study establish a previously unrecognized FOSL1/IKKα/UCHL3 positive feedback loop as a central driver of GBM pathogenesis through activation of NF-κB signaling, providing a promising molecular target for future GBM therapeutic strategies.

Silencing FOSL1, ADAM9, or MMP9 sensitized ATC cells to NK cell-mediated cytotoxicity in vitro and suppressed ATC growth in vivo. Together, these findings highlight the role of FOSL1 in chromatin remodeling of ATC and in dampening cytotoxic functions of NK cells, thereby providing insights into the development of potential cancer therapeutics.

Glioblastoma (GBM) is the most lethal brain tumor, characterized by strong resistance to conventional therapies. Furthermore, vemurafenib, which targets FOSL1, was identified as a potential therapeutic agent against TMZ-resistant GBM in a mouse model. These findings suggest that FOSL1 promotes TMZ chemoresistance by regulating IL-6-pSTAT3Tyr705-mediated stemness in GBM cells, making it a promising therapeutic target to overcome chemoresistance in GBM.

Our work defines the LY6D+ gastric-like cell state as a key driver linking early pre-malignant heterogeneity to PDAC initiation and progression. LY6D represents a pan-stage therapeutic target and a candidate biomarker for early detection and therapeutic targeting.

Moreover, in HGSOC patient-derived xenograft (PDX) models, brigatinib and PARPi combination therapy induced tumor regression and improved overall survival compared with PARPi alone, particularly in models with high FAK and EPHA2. These findings support dual targeting of FAK and EPHA2 as a strategy to achieve effective and durable PARPi responses and identify a promising biomarker-based combinatorial approach using brigatinib and PARPi for HGSOC, particularly the subset characterized by high FAK and EPHA2.

In murine models of MRTX1133-resistant PDAC, BET inhibition cooperated with MRTX1133 to markedly extend overall survival. As BET inhibitors are currently under clinical testing, the combination of MRTX1133 and BET inhibitors warrants further investigation, particularly in tumors that have developed resistance to KRAS inhibition.

Collectively, our findings delineate a novel pro-inflammatory pathway where LncRNA CCAT1 promotes macrophage inflammation by sponging miR-296-3p, thereby derepressing its target FOSL1. Therefore, targeting LncRNA CCAT1 represents a promising therapeutic strategy for treating atherosclerotic cardiovascular disease.

These findings highlight the complexity of the interplay among PARP7, AHR and STING-induced IFN signalling in regulating cancer cell proliferation but also suggest that for some cell lines STING activation might increase their sensitivity to the anti-proliferative effects of RBN2397.

Collectively, these findings unveil a previously unrecognized signaling pathway that coordinately regulates DNA repair fidelity and invasive potential in GBM. Our work proposes the FOSL1‑PRMT1‑CAPS axis as a promising therapeutic target for overcoming radioresistance and improving treatment outcomes in GBM patients.

Clinically, the abundance of LINC00973, miR-6756-3p, EN2, and NOTCH1 in HNSCC samples was correlated and significantly associated with patients' survival. Collectively, our findings revealed a hitherto uncharacterized SE-driven LINC00973-miR-6756-3p-EN2 regulatory axis to facilitate HNSCC progression and highlighted LINC00973 as a promising prognostic biomarker and therapeutic target with considerable translational potential.