The family of GLI zinc finger transcription factors regulates the expression of genes involved in many important cellular processes, notably embryonal development and cellular differentiation. The glioma-associated oncogene homologue 1 (GLI1) isoform, in particular, has attracted much attention because of its frequent activation in many human cancers and its interactions with other signaling pa...

Although Hedgehog signaling plays a major role in GLI1 transcription, there is now evidence suggesting that other pathways/genes, such as c-MYC, may also regulate GLI1 expression. We initiated studies in Burkitt lymphoma cells, which constitutively express c-MYC due to a chromosomal translocation, to determine whether Hedgehog or c-MYC regulates GLI1 expression. We show that all Burkitt lymphom...

Hedgehog (Hh) signaling plays important roles in various development processes. This signaling is necessary for osteoblast formation during endochondral ossification. In contrast to the established roles of Hh signaling in embryonic bone formation, evidence of its roles in adult bone homeostasis is not complete. Here we report the involvement of Gli1, a transcriptional activator induced by Hh s...

The high mobility group box protein SOX9 and the GLI1 transcription factor play protumorigenic roles in pancreatic ductal adenocarcinoma (PDA). In Kras transgenic mice, each of these factors are crucial for the development of PDA precursor lesions. SOX9 transcription is directly regulated by GLI1, but how SOX9 functions downstream of GLI1 is unclear. We observed positive feedback, such that SOX...

Previous studies report controversial role of Hedgehog (HH) signaling in the progression of colon cancer. This study aimed to investigate the expressions of smoothened (SMO) and downstream glioma-associated oncogene homology-1 (GLI1) in colon cancer, colonic adenoma and normal tissues. Colon cancer and normal tissue samples were collected from 49 patients with colon cancer while colonic adenoma...

The Hedgehog (Hh) signaling pathway not only plays important roles in embryogenesis and adult tissue homeostasis, but also in tumorigenesis. Aberrant Hh pathway activation has been reported in a variety of malignant tumors including colon carcinoma. Here, we sought to investigate the regulation of the Hh pathway transcription factor Gli1 by arsenic trioxide and phosphoinositide 3-kinase (PI3K) ...

AIMS The present study is to investigate the effect of the combination of small-interfering RNA (siRNA) treatment with bis-chloroethylnitrosourea (BCNU) on the proliferation and apoptosis of glioma cells. METHODS According to different treatments, glioma U251 cells were randomly divided into blank group, Lipofectamine group, siRNA-Gli1 group, BCNU group and combination group. After treatments...

Activation of the Sonic hedgehog signaling pathway, primarily through mutational inactivation of the PTCH1 gene, is associated with the development of basal cell carcinoma (BCC). Gli1, a member of the Gli family of transcription factors, is expressed in BCC and in transgenic mice targeted expression of Gli1 in basal keratinocytes leads to BCC development. In addition to BCC, previous studies ha...

Aberrant activation of the transcription factor GLI1, a central effector of the Hedgehog (HH) pathway, is associated with several malignancies, including pancreatic ductal adenocarcinoma (PDAC), one of most deadly human cancers. GLI1 has been described as an oncogene in PDAC, making it a promising target for drug therapy. Surprisingly, clinical trials targeting HH/GLI1 axis in advanced PDAC wer...

How cell numbers are determined is not understood. Hedgehog-Gli activity is involved in precursor cell proliferation and stem cell self-renewal, and its deregulation sustains the growth of many human tumours. However, it is not known whether GLI1, the final mediator of Hh signals, controls stem cell numbers, and how its activity is restricted to curtail tumourigenesis. Here we have altered the ...