RUNX3 protein is overexpressed in human basal cell carcinomas

Abstract

Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of b-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/ transforming growth factor-b pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of b-catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.

Histone deacetylases and cancer

“…Paradoxically, Runx3 can act as an oncogene, based on its overexpression in basal cell carcinomas. The effect of acetylation in this setting, however, remains unknown (Salto-Tellez et al, 2006). BTB/POZ repressor proteins that recruit HDACs and co-repressors to chromatin, including BCL6 and PLZF, are targets of protein acetylation.…”

Identification of marker genes including RUNX3 (AML2) that discriminate between different myeloproliferative neoplasms and normal individuals

“…These data suggest that Runx3 is a tumor suppressor gene in the TGFb signaling pathway. However, recently Salto-Tellez et al 8 showed overexpression of RUNX3 protein in human basal cell carcinomas, which suggests that RUNX3 may have a dual role, as a tumor suppressor and as an oncogene.…”

WNT Signaling in Cutaneous Squamous Cell Carcinoma: A Future Treatment Strategy?

“…The role of WNT signaling in a number of non-melanoma skin cancers (NMSCs) including BCC (El-Bahrawy, et al 2003;Salto-Tellez, et al 2006;Yang, et al 2008;Youssef, et al 2012) is already defined, however evidence is also emerging for a role in the development and progression of cSCC too. Here we examine this evidence and investigate the possibility of WNT inhibitors as a novel therapeutic opportunity for disease management of cSCC.…”