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| Home > Publications database > The AHR pathway represses TGFβ-SMAD3 signalling and has a potent tumour suppressive role in SHH medulloblastoma. > print |
| Home > Publications database > The AHR pathway represses TGFβ-SMAD3 signalling and has a potent tumour suppressive role in SHH medulloblastoma. > print |
| 001 | 153094 | ||
| 005 | 20240229123039.0 | ||
| 024 | 7 | _ | |a 10.1038/s41598-019-56876-z |2 doi |
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| 037 | _ | _ | |a DKFZ-2020-00176 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 600 |
| 100 | 1 | _ | |a Sarić, Nemanja |b 0 |
| 245 | _ | _ | |a The AHR pathway represses TGFβ-SMAD3 signalling and has a potent tumour suppressive role in SHH medulloblastoma. |
| 260 | _ | _ | |a [London] |c 2020 |b Macmillan Publishers Limited, part of Springer Nature |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Sonic Hedgehog (SHH) medulloblastomas are brain tumours that arise in the posterior fossa. Cancer-propagating cells (CPCs) provide a reservoir of cells capable of tumour regeneration and relapse post-treatment. Understanding and targeting the mechanisms by which CPCs are maintained and expanded in SHH medulloblastoma could present novel therapeutic opportunities. We identified the aryl hydrocarbon receptor (AHR) pathway as a potent tumour suppressor in a SHH medulloblastoma mouse model. Ahr-deficient tumours and CPCs grown in vitro, showed elevated activation of the TGFβ mediator, SMAD3. Pharmacological inhibition of the TGFβ/SMAD3 signalling axis was sufficient to inhibit the proliferation and promote the differentiation of Ahr-deficient CPCs. Human SHH medulloblastomas with high expression of the AHR repressor (AHRR) exhibited a significantly worse prognosis compared to AHRRlow tumours in two independent patient cohorts. Together, these findings suggest that reduced AHR pathway activity promotes SHH medulloblastoma progression, consistent with a tumour suppressive role for AHR. We propose that TGFβ/SMAD3 inhibition may represent an actionable therapeutic approach for a subset of aggressive SHH medulloblastomas characterised by reduced AHR pathway activity. |
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| 700 | 1 | _ | |a Selby, Matthew |b 1 |
| 700 | 1 | _ | |a Ramaswamy, Vijay |0 0000-0002-6557-895X |b 2 |
| 700 | 1 | _ | |a Kool, Marcel |0 P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8 |b 3 |u dkfz |
| 700 | 1 | _ | |a Stockinger, Brigitta |b 4 |
| 700 | 1 | _ | |a Hogstrand, Christer |0 0000-0001-7545-6975 |b 5 |
| 700 | 1 | _ | |a Williamson, Daniel |b 6 |
| 700 | 1 | _ | |a Marino, Silvia |b 7 |
| 700 | 1 | _ | |a Taylor, Michael D |b 8 |
| 700 | 1 | _ | |a Clifford, Steven C |b 9 |
| 700 | 1 | _ | |a Basson, M Albert |b 10 |
| 773 | _ | _ | |a 10.1038/s41598-019-56876-z |g Vol. 10, no. 1, p. 148 |0 PERI:(DE-600)2615211-3 |n 1 |p 148 |t Scientific reports |v 10 |y 2020 |x 2045-2322 |
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