| First Author | Ichise T | Year | 2019 |
| Journal | J Pathol | Volume | 249 |
| Issue | 1 | Pages | 39-51 |
| PubMed ID | 30953353 | Mgi Jnum | J:279396 |
| Mgi Id | MGI:6362336 | Doi | 10.1002/path.5279 |
| Citation | Ichise T, et al. (2019) CBP/p300 antagonises EGFR-Ras-Erk signalling and suppresses increased Ras-Erk signalling-induced tumour formation in mice. J Pathol 249(1):39-51 |
| abstractText | CREB-binding protein (CBP) and p300 have oncogenic properties; both co-operate with pro-oncogenic transcription factors downstream of Ras-Erk signalling to support cell proliferation. By contrast, missense, truncating and in-frame mutations of CBP/p300 are found frequently in some human cancers, including cutaneous squamous cell carcinomas that originate from epidermal keratinocytes. Data support that dysfunction of CBP/p300 contributes to keratinocyte hyperproliferation and tumourigenesis; however, the mechanism by which dysfunction of CBP/p300 affects keratinocytes is unknown. Here, we used mice harbouring keratinocyte-specific genetic modifications to examine the role of CBP/p300 in the epidermis. While a single copy of either Crebbp or Ep300 was necessary and sufficient for maintaining epidermal development, reduced expression of CBP/p300 strengthened the Ras-Erk signalling-induced hyperplastic phenotype of epidermal keratinocytes. Reduced CBP/p300 expression increased ligand-induced EGFR activity while decreasing basal expression of Mig6, a negative regulator of EGFR. A reduction in CBP/p300, in combination with increased Ras-Erk signalling, also promoted epidermal tumour formation in mice. Thus, our findings support that CBP/p300 acts as a tumour suppressor in epidermal keratinocytes by counteracting EGFR-Ras-Erk signalling. (c) 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
