Non-canonical WNT6/WNT10A signal factor expression in EBV+ post-transplant smooth muscle tumors

Abstract

Post-transplant smooth muscle tumors (PTSMTs) are rare mesenchymal neoplasms which occur after solid organ or haematopoietic stem cell transplantation. PTSMT typically consist of Epstein-Barr-virus (EBV)+ smooth muscle-like cells and show an intermediate malignancy. Their main occurrences are visceral organs, especially the liver, but intracranial appearances are described and associated with a poor prognosis. EBV drives the growth of PTSMT; however, the underlying molecular mechanisms still remain unclear. Gene expression analysis of a set of morphologically similar tumors (leiomyomas, leiomyosarcomas, angioleiomyomas and endothelial haemangiomas) from patients without immunosuppression or EBV-association was performed. Our findings indicate that PTSMT's growth is driven by two factors of the wingless-type protein family: WNT6 and WNT10A. We are first to report that in PTSMTs, a non-canonical activation of WNT, independent of beta-catenin, drives tumor cell proliferation via MTOR/AKT1, MYC and Cyclin D2.