FOSL2 (FOS Like 2)

Consequently, this FOSL2-deficient state profoundly sensitizes AML cells to conventional chemotherapies, including doxorubicin and cytarabine, as well as ER stress-inducing agents. Collectively, these findings establish that FOSL2 orchestrates a key proteostatic vulnerability. Targeting the FOSL2-ERAD axis represents a compelling therapeutic strategy to dismantle chemoresistance and improve patient outcomes in AML.

SOX9 and TNFAIP3 emerge as key mediators linking persistent epigenetic alterations with immune remodeling in HCV-related HCC, and as potential non-invasive biomarkers for evaluation of HCC risk and post-DAA surveillance.

These findings suggest that FOSL2 may contribute to treatment response heterogeneity by shaping the tumor immune microenvironment, offering novel insights into resistance mechanisms and uncovering potential strategies to enhance the efficacy of hormone therapy in PCa. Implications: Targeting FOSL2-mediated PD-L1 regulation offers a promising strategy to overcome immune microenvironment-mediated resistance and improve the therapeutic efficacy of androgen-targeted therapy in PCa.

Our results also highlighted transcription factors IKZF1, FOSL2, and FOXO1 in the less activated γδ T cells and IRF1, KLF2, and BHLHE40 in the effector γδ T cells that plausibly regulated the differential activation state. Together, our results offer a systems-level view of the signaling and transcriptional programs governing γδ T cell phenotypes in CRC and provide a foundation for γδ T cell-based immunotherapies with enhanced antitumor functions.

Critically, ALDH3A1 elevation selectively curbs EBV-positive tumor growth, exploiting an infection-specific vulnerability in redox signaling. Thus, our findings integrate EBV-driven redox remodeling with Wnt/β-catenin signaling activation and propose ALDH3A1 induction as a promising therapeutic strategy for EBV-associated carcinomas.

We nominate ANXA1 and HMOX1 as surrogate cell surface markers for a subpopulation we term malignancy associated GAMs (mGAMs) which possess distinct pro-tumorigenic properties, share partial ontogeny with peripheral blood monocytes, and are enriched in newly transformed regions of glioma. mGAMs potentially play a pivotal role in glioma progression and represent a plausible therapeutic target.

Exploiting this 'death switch' offers a novel therapeutic framework through three principal strategies: (1) inducing pyroptosis to eliminate apoptosis-resistant cells, (2) utilizing pyroptosis-induced inflammation to enhance immune checkpoint inhibitor efficacy, and (3) developing targeted therapeutics that directly modulate these switch molecules. Although controlling pyroptosis-associated inflammation remains challenging, understanding and manipulating the apoptosis-to-pyroptosis transition provides an innovative approach to overcome drug resistance and develop more effective cancer treatments.

This study identifies a previously unrecognized master regulator CCNC that functions as a suppressor of CD155-mediated cancer immune evasion. The findings of this study suggest that tumors with low CCNC expression may be resistant to monotherapy and highlight a combination immunotherapy (TIGIT/PD-1 co-blockade) as a promising anti-cancer therapeutic strategy to overcome immune evasion in CCNC-deficient tumors.

Crucially, we demonstrate that mitogen-activated protein kinase kinase (MEK) inhibitors effectively suppress the MAP3K8-MEK signaling cascade and significantly mitigated inflammatory pathogenesis in an ex vivo culture assay. Our findings provide critical insights into the virus-host interactions underpinning HAM and propose the MAP3K8-MEK-ERK axis as a promising therapeutic target for this challenging condition.

Treatment with the AP-1 inhibitor T5224 reduced proliferation of A549 cells. Moreover, knockdown of L1CAM attenuated the tumor-promoting effects of FOSL2 overexpression, indicating that L1CAM contributes to the oncogenic activity of FOSL2, possibly by mediating activation of the PI3K/AKT/mTOR signaling pathway.

Functionally, COL8A1 promotes mesenchymal phenotypes, enhances CRC cell migration and invasion in vitro, and promotes tumor growth in vivo. Collectively, our findings uncover a previously unrecognized FOSL2-COL8A1-EMT regulatory axis that fuels CRC progression and metastasis, providing novel mechanistic insights into EMT maintenance and nominating COL8A1 as a promising prognostic biomarker and therapeutic target for advanced colorectal cancer.

Moreover, we determined that PREX2 played a malignant role in ccRCC with sarcomatoid differentiation in vitro and in vivo, facilitating tumor progression by inhibiting PTEN and activating the PI3K/AKT pathway. This study demonstrated the comprehensive gene expression and DNA regulation information of ccRCC with sarcomatoid differentiation, highlighting its malignant characteristics, thereby offering novel insights for the diagnosis and treatment of sarcomatoid ccRCC.