TGFBR2 (Transforming Growth Factor Beta Receptor 2)

Our findings demonstrate that ALB functions as a novel inhibitor of TβRs, effectively suppressing tumor growth and lung metastasis by inhibiting the EMT process both in vitro and in vivo.

Together, these results indicate that deuterium concentration acts as a bidirectional modulator of gene expression programs in the A549 model, with enrichment broadly elevating oncogenic expression and moderate depletion associated with selective downregulation of genes linked to resistance, signaling, and invasive behavior. Significance: Deuterium depletion is associated with reduced expression of genes involved in multidrug resistance, growth-factor signaling, and transcriptional amplification, revealing deuterium-responsive transcriptional vulnerabilities within the A549 lung adenocarcinoma model.

Combinatorial gene KOs in CAFs reveals a circuit where these Col18a1hi CAFs reshape the TME by recruiting Siglec-Fhi neutrophils via Cxcl5 expression, and where this Col18a1hi CAF cell state is dependent on TNFR1 and canonical Wnt signaling. Together, a fast, affordable, and modular engineering method is demonstrated, allowing discovery of modified fibroblast identities and local intercellular relationships in the TME.

In vivo administration of exosomes derived from S1P-treated murine breast cancer cells in a breast cancer allograft model markedly promoted tumor growth and heightened CD8 T cell exhaustion, whereas exosomes from TGFBR2-silenced, S1P-treated cells exerted the reverse effect, underscoring the pivotal role of the S1P-TGFBR2 axis in modulating the tumor microenvironment. These findings suggest that targeting the S1P-TGFBR2 pathway could enhance antitumor immunity in breast cancer.

Our study provides insight into the altered epigenetic gene control landscape and TME processes of the NFPA tumor phenotype. Our data are freely available at https://rstudio-connect.hpc.mssm.edu/nfpa_browser/.

The present epigenetic memory in BA-SHED implies that BA-SHED imprint bile duct deficiency through TGFBR2 dysregulated by the HNF6 promoter activation epigenetically. Thus, BA-SHED are a potential model for expanding our knowledge in BA research.

Moreover, increased matrix stiffness was found to induce YEATS2 expression through augmenting the binding of HIF-1α to the YEATS2 promoter. Collectively, these results delineate a novel YEATS2-TGFBR2-TAZ-AKT signaling axis that connects matrix stiffness to metabolic reprogramming and HCC progression, highlighting YEATS2 as a potential therapeutic target for HCC.

This study delineated transcriptional differences between primary tumors and MetLNs in lung cancer, thereby providing a foundation for further exploration of LN metastasis.

P1/2, N=28, Not yet recruiting, M.D. Anderson Cancer Center

Strikingly, hyaluronidase expression in WKTP cells significantly suppresses liver metastasis. Here we show the critical role of ligand-dependent Wnt signaling and Has2-mediated hyaluronan deposition in metastasis, offering potential therapeutic strategy against gastric cancer metastasis.

TGFBI knockdown or GDF15 inhibition results in a decrease in functional proteins associated with stemness maintenance, which suppresses bladder CSCs' self-renewal and effectively improves the efficacy of chemotherapy. Together, these findings demonstrate the pivotal role of TGFBI in BLCA's stemness maintenance and BLCA progression, highlighting that the inhibition of the TGFBI/GDF15 axis is a potential therapeutic strategy for the amelioration of cancer chemotherapy.

No functionally deleterious driver gene mutations were identified that were attributed to treatment, although radiated PDACs had significantly greater genomic complexity and distinct mutational signatures compared to PDACs managed by chemotherapy. These findings provide a high-level profile of the genetic features distinguishing locally advanced from metastatic PDAC, potentially serving as a biomarker of borderline resectable or locally advanced PDACs most likely to benefit from neoadjuvant chemoradiation.