The tendon enthesis originates from a specific pool of hedgehog-active Gli1+ progenitor cells that differentiate and produce mineralized fibrocartilage. The current study investigated the regenerative capacity of this cell population by comparing the responses of early postnatal and mature entheses to injury. Lineage tracing studies demonstrated that the original Gli1+ cell population had the c...

Few studies have evaluated Hedgehog (Hh) signaling pathway activation in different types of ovarian tumors including benign, borderline and malignant ovarian tumors. The present study investigated the expression of Hh signaling pathway components (SHH, SMO, PTCH, and GLI1) in 193 ovarian epithelial tumor specimens (including 147 malignant epithelial ovarian cancers, 30 borderline ovarian tumors...

To improve the pharmacokinetics and to study the anti-cervical cancer and anti-stem cells (CSCs) mechanism of Quinacrine (QC), a spherical nano particle of QC (i.e. NQC) was prepared and characterized. QC and NQC showed higher cytotoxicity in multiple cancer cells than the normal epithelial cells. NQC exhibited more toxicity in cervical cancer cells and its CSCs than QC. A dose-dependent decrea...

Hedgehog (HH) signaling is one of the key pathways with major significance for embryogenesis, tumorigenesis, and stem cell maintenance. Glioma-associated oncogene 1 (GLI1) is a transcription factor that acts as the terminal signaling effector but also represents a pathway target gene. Here we report the identification and functional properties of novel GLI1 splice variants generated by skipping...

Hedgehog signaling controls proliferation of cerebellar granule cell precursors (GCPs) and its aberrant activation is a leading cause of Medulloblastoma, the most frequent pediatric brain tumor. We show here that the energy sensor AMPK inhibits Hh signaling by phosphorylating a single residue of human Gli1 that is not conserved in other species. Studies with selective agonists and genetic delet...

Glioma-associated oncogene 1 (Gli1) is a critical transcriptional factor of Sonic hedgehog pathway which has been proved to participate in the initiation and progression of tumor in mammalians. However, its clinical value in breast cancer remains unknown. Thus, a meta-analysis was performed to clarify the association of Gli1 over-expression, clinic-pathological characteristics, molecular subtyp...

Chronic kidney disease is characterized by interstitial fibrosis and proliferation of scar-secreting myofibroblasts, ultimately leading to end-stage renal disease. The hedgehog (Hh) pathway transcriptional effectors GLI1 and GLI2 are expressed in myofibroblast progenitors; however, the role of these effectors during fibrogenesis is poorly understood. Here, we demonstrated that GLI2, but not GLI...

BACKGROUND/AIMS Resistance of leukemia stem cells (LSCs) to chemotherapy in patients with acute myeloid leukemia (AML) causes relapse of disease. Hedgehog (Hh) signaling plays a critical role in the maintenance and differentiation of cancer stem cells. Yet its role in AML remains controversial. The purpose of the present study is to investigate the role of GLI1, the transcriptional activator of...

Jagged2 is closely associated with numerous congenital diseases and has an important role in multiple malignancies. It has been identified that Jagged2 is a sonic hedgehog‑regulated factor. However, its expression and correlation with Gli1 in hepatocellular carcinoma (HCC) remain unknown. A total of 58 samples of surgically resected paired HCC and normal tumor‑adjacent tissues were collected, a...

The canonical hedgehog (HH) pathway is a multicomponent signaling cascade (HH, protein patched homolog 1 (PTCH1), smoothened (SMO)) that plays a pivotal role during embryonic development through activation of downstream effector molecules, namely glioma-associated oncogene homolog 1 (GLI1), GLI2 and GLI3. Activation of GLIs must be tightly regulated as they modulate target genes which control t...