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|Title:||A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma|
Browne, Gareth J.
Saldanha, Gerald Saldanha
Pringle, J. Howard
|Publisher:||Elsevier (Cell Press)|
|Citation:||Cancer Cell, 2013, 24 (4), pp. 466-480|
|Abstract:||Aberrant expression of embryonic epithelial-mesenchymal transition-inducing transcription factors (EMTTFs) in epithelial cells triggers EMT, neoplastic transformation, stemness, and metastatic dissemination. We found that regulation and functions of EMT-TFs are different in malignant melanoma. SNAIL2 and ZEB2 transcription factors are expressed in normal melanocytes and behave as tumor-suppressor proteins by activating an MITF-dependent melanocyte differentiation program. In response to NRAS/BRAF activation, EMT-TF network undergoes a profound reorganization in favor of TWIST1 and ZEB1. This reversible switch cooperates with BRAF in promoting dedifferentiation and neoplastic transformation of melanocytes. We detected EMT-TF reprogramming in late-stage melanoma in association with enhanced phospho-ERK levels. This switch results in E-cadherin loss, enhanced invasion, and constitutes an independent factor of poor prognosis in melanoma patients.|
|Description:||Full text of this item is not currently available on the LRA. The final published version may be available through the links above.|
|Appears in Collections:||Published Articles, Dept. of Cancer Studies and Molecular Medicine|
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