A Switch in the Expression of Embryonic EMT-Inducers Drives the Development of Malignant Melanoma

被引：472

作者：

Caramel, Julie ^{[1
,2
,3
,4
,5
,6
]}

Papadogeorgakis, Eftychios ^{[7
]}

Hill, Louise ^{[1
,2
,3
,4
,5
,6
]}

Browne, Gareth J. ^{[7
]}

Richard, Geoffrey ^{[1
,2
,3
,4
,5
,6
]}

Wierinckx, Anne ^{[1
,2
,3
,4
,5
,6
,8
]}

Saldanha, Gerald ^{[7
]}

Osborne, Joy ^{[9
]}

Hutchinson, Peter ^{[7
]}

Tse, Gina ^{[7
]}

Lachuer, Joel ^{[1
,2
,3
,4
,5
,6
,8
]}

Puisieux, Alain ^{[1
,2
,3
,4
,5
,6
,10
]}

Pringle, J. Howard ^{[7
]}

Ansieau, Stephane ^{[1
,2
,3
,4
,5
,6
]}

Tulchinsky, Eugene ^{[7
]}

机构：

[1] Ctr Rech Cancerol Lyon, INSERM, UMR S1052, F-69008 Lyon, France

[2] Ctr Rech Cancerol Lyon, CNRS, UMR5286, F-69008 Lyon, France

[3] LabEX DEVweCAN, F-69008 Lyon, France

[4] Univ Lyon 1, F-69008 Lyon, France

[5] Univ Lyon, F-69008 Lyon, France

[6] Ctr Leon Berard, F-69008 Lyon, France

[7] Univ Leicester, Dept Canc Studies & Mol Med, Leicester LE1 5WW, Leics, England

[8] ProfileXpert, F-69500 Bron, France

[9] Univ Hosp Leicester NHS Trust, Dept Dermatol, Leicester LE1 5WW, Leics, England

[10] Inst Univ France, F-75006 Paris, France

来源：

CANCER CELL | 2013年 / 24卷 / 04期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; CANCER STEM-CELLS; BREAST-CANCER; METASTATIC COLONIZATION; TRANSCRIPTION FACTOR; TUMOR PROGRESSION; BRAF MUTATION; MOUSE; MITF; TRANSFORMATION;

D O I：

10.1016/j.ccr.2013.08.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Aberrant expression of embryonic epithelial-mesenchymal transition-inducing transcription factors (EMTTFs) in epithelial cells triggers EMT, neoplastic transformation, sternness, 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 nielanocyte 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.

引用

页码：466 / 480

页数：15

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