GLI1 (GLI Family Zinc Finger 1)

Increased levels of Gli3 repressor (Gli3-REP) and decreased GSK-3β phosphorylation further confirmed Hedgehog pathway inhibition. In conclusion, the current study provides the first evidence that CAN, CGA, and their combination modulate the Hedgehog pathway, suggesting their potential as novel therapeutic strategies for IPF.

Furthermore, flow cytometry and colony formation assays revealed that PCZ attenuates and reduces the apoptotic/necrotic effects of ATO. In conclusion, PCZ synergistically and effectively reduces the adverse cytotoxic effects of ATO in lung cancer cells, providing a promising new therapeutic strategy for lung cancer treatment.

Then, the hypoxic PASMCs were transfected si-GLI1 alone or together with HDAC1-OE, and further confirm that GLI1 promotes hypoxia induced pyroptosis and abnormal proliferation of PASMCs by upregulating HDAC1 protein expression. In addition, we constructed a PAH rat model, and found that GLI1 silenced PAH rats had reduced expression of markers related to pyroptosis and smooth muscle cell proliferation in the lung tissue, and the lung injury of rats was reduced, and the lung function was significantly improved, suggesting that GLI1 silencing is beneficial to PAH in rats.

Our findings reveal that STING exerts its pro-fibrotic effects primarily through EV-mediated intercellular trafficking rather than direct intracellular signaling. This study defines a critical tubular cell-STING-EV-fibroblast communication loop that drives the AKI-to-CKD transition and highlights therapeutic opportunities targeting EV-STING release or SMO-GLI-1 signaling to prevent chronic kidney disease.

The breakpoint was identical to those in the previously reported cases. Taken together, these findings suggest that PTCH1::GLI2 fusion may define a distinctive subtype of gastric mesenchymal tumors within the GLI1/GLI2-altered spectrum.

By comparing treatment and culture context independently, cyclopamine-mediated SHH inhibition and astrocyte-dependent signals use distinct but interacting effects on cell behavior...Astrocyte co-culture significantly modulates the molecular and phenotypic response of GBM cells to SHH inhibition, reshaping apoptotic and proliferative behaviors in both CSCs and bulk populations. These findings highlight the critical importance of the tumor microenvironment in therapeutic response and suggest that effective targeting of SHH signaling may require models that account for astroglial interactions.

CAV1 gene silencing by siRNA validated its role in maintenance of stem-like phenotype and metabolic alterations of GBM spheroids. Collectively, this study demonstrated the regulatory role of Caveolin1 and cholesterol in maintaining stem-like characteristics of GBM spheroids and the importance of tumor models in better understanding of the molecular mechanism of GBM.Key words: Glioblastoma, cholesterol biosynthesis, stemness, Caveolin1, DNMT1, KDM5A, Gli1.

The findings highlight GD's potential as a promising therapeutic candidate for PDAC, with the ability to target both bulk tumor cells and PCSCs. By simultaneously suppressing tumor growth, stemness, and metastatic spread, GD may contribute to more effective treatment strategies and improved patient outcomes.

NUPR1 and MGMT promoter hypermethylation was associated with a favorable response to temozolomide therapy. Patients with NUPR1 and MGMT hypermethylation exhibited extended OS and PFS compared to those with hypomethylation levels, whereas GLI1 and NDRG2 hypermethylation were linked to shorter PFS. In conclusion, the multi-faceted epigenetic panel adopted in the current study captures different aspects of GBM biology and moves towards a more comprehensive model that reflects the molecular heterogeneity of GBM as insights for personalized therapy.

The univariate analysis revealed that lower OS was associated with nGLI IS >6 [hazard ratio (HR), 1.50; 95% CI, 1.44-14.13; P=0.010] and ncGLI1 IS 6 (HR, 1.53; 95% CI, 1.23-17.49; P=0.023). The present study results demonstrated the utility of IS in evaluating the prognostic impact of SETD2 and GLI1 expression in patients with LACC.

The Gli-targeting agent GANT61 may inhibit ALK + ALCL cell growth, trigger cell cycle arrest and induce apoptosis through Gli1 inhibition, potentially leading to PIK3IP1 upregulation and subsequent attenuation of PI3K/Akt pathway activity. These findings indicate that the Hh-PIK3IP1-Akt signaling axis may participate in ALK + ALCL tumorigenesis, showing that conventional target drugs can be employed for ALK + ALCL treatment.

In this review, we summarize advances in our understanding of Hh-mediated cell death in gastrointestinal cancers and the role and mechanisms, and highlight the underlying therapeutic opportunities. These new findings advance the rapidly expanding field of translational cancer research focused on the Hh signaling pathway.