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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Riaz, Syeda Kiran Khan, Jahangir Sarwar Shah, Syed Tahir Abbas Wang, Fen Ye, Lin Jiang, Wen G. Malik, Muhammad Faraz Arshad |
| Abstract | Background Dysregulation of hedgehog pathway is observed in numerous cancers. Relevance of hedgehog pathway genes in cancer cohort and inhibition of its downstream effector (GLI1) towards metastasis in cell lines are explored in the study. Method One hundred fifty fresh tumours of breast cancer patients were collected for the study. Based on differential expression, panel of 6 key regulators of the pathway (SHH, DHH, IHH, PTCH1, SMO and GLI1) in microarray datasets were identified. Expressional profiles of aforementioned genes were later correlated with clinico-pathological parameters in Pakistani breast cancer cohort at transcript and protein levels. In addition, GLI1 over expressing breast cancer cell lines (MDA-MB-231 and MCF-7) were treated with GANT61 to explore its probable effects on metastasis. Result SHH, DHH, PTCH1 and GLI1 were significantly over-expressed in tumours as compared with respective normal mammary tissues. A significant correlation of SHH, DHH and GLI1 expression with advanced tumour size, stages, grades, nodal involvement and distant metastasis was observed (pā<ā0.05). Over-expression of SHH, DHH and GLI1 was significantly related with patients having early onset and pre-menopausal status. Of note, hedgehog pathway was frequently up regulated in luminal B and triple negative breast cancer affected women. In addition, positive correlations were observed among aforementioned members of pathway and Ki67 (r-value: 0.63ā0.78) emphasizing their role towards disease progression. Exposure of GANT61 (inhibitor for GLI1) significantly restricted cell proliferation, reduced cell motility and invasion. Conclusion Role of activated hedgehog pathway in breast cancer metastasis provides a novel target for cancer therapy against aggressive cancer subtypes. |
| Related Links | https://biosignaling.biomedcentral.com/counter/pdf/10.1186/s12964-017-0213-y.pdf |
| Ending Page | 12 |
| Page Count | 12 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s12964-017-0213-y |
| Journal | Cell Communication and Signaling |
| Issue Number | 1 |
| Volume Number | 16 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2018-01-08 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Protein-Ligand Interactions Receptors Cytokines and Growth Factors Breast cancer Hedgehog pathway SHH DHH GLI1 GANT61 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry Cell Biology Molecular Biology |
| Journal Impact Factor | 8.2/2023 |
| 5-Year Journal Impact Factor | 8/2023 |
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