Non-canonical Hedgehog Signaling Pathway in Cancer: Activation of GLI Transcription Factors Beyond Smoothened

The Hedgehog-GLI (HH-GLI) pathway is a highly conserved signaling that plays a critical role in controlling cell specification, cell-cell interaction and tissue patterning during embryonic development. Canonical activation of HH-GLI signaling occurs through binding of HH ligands to the twelve-pass transmembrane receptor Patched 1 (PTCH1), which derepresses the seven-pass transmembrane G protein-coupled receptor Smoothened (SMO). Thus, active SMO initiates a complex intracellular cascade that leads to the activation of the three GLI transcription factors, the final effectors of the HH-GLI pathway. Aberrant activation of this signaling has been implicated in a wide variety of tumors, such as those of the brain, skin, breast, gastrointestinal, lung, pancreas, prostate and ovary. In several of these cases, activation of HH-GLI signaling is mediated by overproduction of HH ligands (e.g. prostate cancer), loss-of-function mutations in PTCH1 or gain-of-function mutations in SMO, which occur in the majority of basal cell carcinoma (BCC), SHH-subtype medulloblastoma and rhabdomyosarcoma. Besides the classical canonical ligand-PTCH1-SMO route, mounting evidence points toward additional, non canonical ways of GLI activation in cancer. By non canonical we refer to all those mechanisms of activation of the GLI transcription factors occurring independently of SMO. Often, in a give cancer type canonical and non canonical activation of HH-GLI signaling co-exist, and in some cancer types, m...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research

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CONCLUSION: These findings indicate increased resistance of E. coli to ciprofloxacin in comparison with prior studies. Further research in this field will increase our knowledge and more effective exposure to the antibiotic resistance of the pathogenic microorganisms. PMID: 31198116 [PubMed - as supplied by publisher]
Source: Recent Patents on Anti-Infective Drug Discovery - Category: Infectious Diseases Tags: Recent Pat Antiinfect Drug Discov Source Type: research
CONCLUSIONS: During antihypertensive treatment, several dermatological reactions may occur. Clinicians should inform their patients of the increased risk of cutaneous lesions associated with the use of these drugs, and perform periodic examination of the skin. PMID: 31195782 [PubMed - as supplied by publisher]
Source: Giornale Italiano di Dermatologia e Venereologia - Category: Dermatology Tags: G Ital Dermatol Venereol Source Type: research
CONCLUSIONS: The traumatic aspects following the diagnosis of melanoma burst powerfully into the life of these patients, who show different reactions, also according to gender. PMID: 31195781 [PubMed - as supplied by publisher]
Source: Giornale Italiano di Dermatologia e Venereologia - Category: Dermatology Tags: G Ital Dermatol Venereol Source Type: research
In this study, MCF-7 and T47D cells were treated with inhibitors of 17β-HSD1, 17β-HSD7, aromatase or steroid sulfatase (STS), then mRNA levels of 17β-HSD7, STS, 11β-HSD 2, estrogen receptors α (ERα) and androgen receptor (AR) were determined by Q-PCR. ER negative cell line MDA-MB-231 was used as a negative control. Our results demonstrate that 17β-HSD7, STS and 11β-HSD2 are all regulated by the same estrogen estradiol via ERα. When the gene of ERα (ESR1) was knocked down, there was no longer significant mutual regulation of these enzymes.Our results demonstrate that imp...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research
This study demonstrated promising anticancer and antibacterial effects of Artemia salina egg extracts. Our results suggest that pure bioactive compounds obtained from Artemia salina eggs can provide new insights into the mechanisms of colon and skin cancer, as well as Pseudomonas aeruginosa inhibition. PMID: 31198432 [PubMed]
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
Publication date: Available online 14 June 2019Source: Urology Case ReportsAuthor(s): C. García Alvarez, R.J. González Alvarez, A.C. Plata Bello, H. Alvarez-Argüelles Cabrera, D. Castro Díaz, T. Concepción MasipAbstractA 35-year-old male patient was admitted to our hospital for urachal carcinoma with oligometastatic bone disease. He received a surgical resection through the umbilical area, urachal ligament and bladder dome (partial cystectomy) and adjuvant chemotherapy based on cisplatin-gemcitabine regimens together zoledronic acid with a good tolerance, no toxicity. Nine months after surg...
Source: Urology Case Reports - Category: Urology & Nephrology Source Type: research
Abstract Trophinin-associated protein (TROAP) is a cytoplasmic protein required for microtubular cytoskeleton regulation and spindle assembly, and its expression plays a critical role in the initiation and progression of various types of cancer. However, little is known about the role of TROAP in breast cancer (BC). TROAP mRNA expression levels and clinical data from Gene Expression Omnibus (GEO) datasets (GSE42568, 104 BC patients; GSE1456, 159 BC patients; and GSE21653, 266 BC patients) were analyzed by the R2: Genomics Analysis and Visualization Platform to estimate overall survival (OS). We also analyzed the g...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
ConclusionsStress conditions induced by locoregional therapies stimulated hCSC enrichment and proliferation, which could be suppressed by niclosamide and inhibitors of pathways important for hCSC renewal. Future studies will determine whether combining locoregional therapies with adjuvant hCSC inhibitors reduces HCC recurrence.
Source: Journal of Vascular and Interventional Radiology - Category: Radiology Source Type: research
ConclusionTOL methodology allowed effective training of both groups of readers. The iterative nature of individual training ensured production of user-friendly materials including frequently-asked-questions sheets. It allowed for each person to feel that their views were fully listened to and incorporated into the training package, allowing for training materials with high face validity.
Source: European Journal of Radiology Open - Category: Radiology Source Type: research
We present eight patients treated with wide resection (3 myxofibrosarcomas, 2 malignant melanomas, 1 spindle cell sarcoma, 1 basal cell carcinoma, and 1 exulcerated lipoma). No complications were observed using this technique. An intraoperative local control, confirmed histologically, was achieved in all patients. Tumor covering could help local tumor control at fungating tumor resection.
Source: Orthopaedics and Traumatology: Surgery and Research - Category: Orthopaedics Source Type: research
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