EMT and MET-related processes in non-epithelial tumors: importance for disease progression, prognosis and therapeutic opportunities.

EMT and MET-related processes in non-epithelial tumors: importance for disease progression, prognosis and therapeutic opportunities.

Mol Oncol. 2017 May 28;:

Authors: Kahlert UD, Joseph JV, Kruyt FAE

Abstract
The epithelial-to mesenchymal (EMT) process is increasingly recognized for playing a key role in the progression, dissemination and therapy resistance of epithelial tumors. Accumulating evidence suggests that EMT inducers also lead to a gain in mesenchymal properties and promote malignancy of non-epithelial tumors. In this review we present and discuss current findings, illustrating the importance of EMT inducers in tumors originating from non-epithelial/ mesenchymal tissues, including: brain tumors, hematopoietic malignancies and sarcomas. Among these tumors, the involvement of mesenchymal transition (MT) has been most extensively investigated in glioblastoma, providing proof for cell autonomous and microenvironment-derived stimuli that provoke EMT-like processes that regulate stem cell, invasive and immunogenic properties as well as therapy resistance. The involvement of prominent EMT transcription factor families, such as TWIST, SNAI and ZEB, in promoting therapy resistance and tumor aggressiveness has also been reported in lymphomas, leukemias and sarcomas. A reverse process, resembling mesenchymal-to epithelial transition (MET), seems particularly relevant for sarcomas, where (partial) epithelial differentiation is linked to less aggressive tumors and a better patient prognosis. Overall, a hybrid model in which more stable epithelial and mesenchymal intermediates exist likely extends to the biology of tumors originating from sources other than the epithelium. Deeper investigation and understanding of the EMT/MET machinery in non-epithelial tumors will shed light on the pathogenesis of these tumors, potentially paving the way towards the identification of clinically relevant biomarkers for prognosis and future therapeutic targets.

PMID: 28556516 [PubMed - as supplied by publisher]

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