KRAS Promotes GLI2-Dependent Transcription during Pancreatic Carcinogenesis.

Aberrant activation of GLI transcription factors has been implicated in the pathogenesis of different tumor types including pancreatic ductal adenocarcinoma. However, the mechanistic link with established drivers of this disease remains in part elusive. In this study, using a new genetically engineered mouse model overexpressing constitutively active mouse form of GLI2 and a combination of genome-wide assays, we provide evidence of a novel mechanism underlying the interplay between KRAS, a major driver of pancreatic ductal adenocarcinoma development, and GLI2 to control oncogenic gene expression.

Circular and Fusion RNAs in Medulloblastoma Development.

The cerebellar cancer medulloblastoma is the most common childhood cancer in the brain. . RNA sequencing of 81 human biospecimens of medulloblastoma using pipelines to detect circular and fusion RNAs.

Circular RNAs in Hedgehog Signaling Activation and Hedgehog-Mediated Medulloblastoma Tumors.

Within the past decade, circular RNAs have largely emerged as novel regulators of human biology, including brain function and cancer development. On the other hand, the Hedgehog pathway has established roles in regulating biological processes, including tumorigenesis. Here, the circular RNA transcriptome, in the context of Hedgehog signaling activation of medulloblastoma Daoy and human embryonic palatal mesenchyme HEPM cells, was determined.

RITA downregulates Hedgehog-GLI in medulloblastoma and rhabdomyosarcoma via JNK-dependent but p53-independent mechanism.

Overactivation of the Hedgehog (HH) signaling pathway is implicated in many cancers. In this study, we demonstrate that the small molecule RITA, a p53 activator, effectively downregulates HH signaling in human medulloblastoma and rhabdomyosarcoma cells irrespective of p53. This is mediated by a ROS-independent activation of the MAP kinase JNK.

Identification of novel GLI1 target genes and regulatory circuits in human cancer cells.

Hedgehog (HH) signaling is involved in many physiological processes, and pathway deregulation can result in a wide range of malignancies. Glioma-associated oncogene 1 (GLI1) is a transcription factor and a terminal effector of the HH cascade. Despite its crucial role in tumorigenesis, our understanding of the GLI1 cellular targets is quite limited.