GLI2 overexpression

A chemotherapy regimen includes a combination of high-dose Methotrexate (MTX), doxorubicin, and cisplatin...CUR and MTX combined determined a β-Catenin decrease and a trend toward reducing NF-kB and matrix metalloproteinases (MMP-2 and MMP-9). Our findings suggest CUR as a support to OS treatment, improving outcomes and reducing the adverse effects of current therapies.

Using flow cytometry, we observed distinct changes in fat pad macrophage populations, with a particular increase in M2-like macrophages. Taken together, we find that overexpression of Gli2 in DDLPS cells alters their differentiation capacity and interactions between tumor cells and macrophages, highlighting a novel role for this developmental transcription factor in liposarcoma pathogenesis.

However, the above effects were largely abrogated by CDH6 knockdown. In conclusion, the present study suggested that the novel GLI2/CDH6 axis could enhance the migration, invasion and mitochondrial fission of STAD cells.

Similarly, the combination of GLI2 and NMYC was neither sufficient for the development of SHH-MB. We therefore assume that the development of childhood SHH-MB in mice is either occurring in cellular origins outside the hGFAP-positive lineage or needs additional genetic drivers.

Down-regulation of Wnt antagonist secreted frizzled-related protein 4 (sFRP4) in GBM and GSCs, indicating activation of the Wnt/β-catenin pathway, which could be involved in the conversion of iPSCs to CSCs. From future perspectives, our study will help in the creation of a rapid cell-based platform for understanding the complexity of GBM.

Cholangiocarcinoma cells regulated TAM polarization and TGF-β1 secretion via a paracrine SHH signaling pathway, and in turn, TAMs promoted the growth, EMT, and ER homeostasis of cholangiocarcinoma cells via TGF-β1.

Our study provides insight into the unique and overlapping transcriptional output of the GLI proteins in melanoma. We suggest that our findings could provide new potential targets to consider while designing melanoma-targeted therapy.

Consequently, SSB1 (30 mg/kg, ip) and SSD (10 mg/kg, ip) displayed excellent in vivo inhibitory activity in MB allografts, and the tumor growth inhibition ratios were approximately 50% and 70%, respectively. Our findings, thus, identify SSB1 and SSD significantly inhibit tumor growth in MB models by inhibiting the Hedgehog pathway through targeting SMO.

Cisplatin (DDP) resistance remains a key challenge in improving the clinical outcome of patients with ovarian cancer (OC)...In cells stably overexpressing Gli2, treatment with gradient concentrations of verapamil, an MDR1 inhibitor, significantly inhibited MDR1 expression...We identified a mechanism by which Hedgehog-Gli signaling regulates OC chemoresistance by modulating MDR1 expression. Hence, Gli2 and MDR1 are potential biomarkers and therapeutic targets in patients with chemoresistant OC.

Our findings point towards the importance of a tumor-promoting inflammatory environment in leukemia progression, as indicated by several of the herein identified differentially expressed genes. Together, this knowledge provides the foundation for novel personalized drug targets and has the potential to maximize the benefit of current treatments, to improve cure rates in AML.

miR-636 mediates the activation of the Hh pathway via binding to Gli2, thus inhibiting EMT, suppressing cell proliferation and migration of OVC.

This is the first study of both adult and pediatric AML incorporating WGS and RNA-seq analyses on sequential AML samples. Knowledge gathered from this study has provided critical new insights into the biologic basis of this complex disease and will hopefully help to pave the way for improved and individualized treatment strategies.