Premium
Loss of neural crest‐associated gene FOXD1 impairs melanoma invasion and migration via RAC1B downregulation
Author(s) -
Wu Huizi,
Larribère Lionel,
Sun Qian,
Novak Daniel,
Sachindra Sachindra,
Granados Karol,
Umansky Viktor,
Utikal Jochen
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31799
Subject(s) - neural crest , downregulation and upregulation , gene knockdown , melanoma , biology , microphthalmia associated transcription factor , cancer research , zebrafish , mmp9 , cell migration , transcription factor , microbiology and biotechnology , cell , gene , genetics
Recent studies suggest that malignant melanoma heterogeneity includes subpopulations of cells with features of multipotent neural crest (NC) cells. Zebrafish and mouse models have shown that reactivation of neural crest‐specific pathways during transformation determines the invasiveness of melanoma cells. In our study, we show that the neural crest‐associated transcription factor FOXD1 plays a key role in the invasion and the migration capacities of metastatic melanomas both in vivo and in vitro . Gene expression profiling analysis identified both an upregulation of FOXD1 in NC and melanoma cells, as well as a downregulation of several genes related to cell invasion in FOXD1 knockdown cells, including MMP9 and RAC1B . Furthermore, we demonstrate that knockdown of RAC1B a tumor‐specific isoform of RAC1 , significantly impaired melanoma cell migration and invasion and could abrogate enhanced invasiveness induced by FOXD1 overexpression. We conclude that FOXD1 may influence invasion and migration via indirect regulation of MMP9 and RAC1B alternative splicing in melanoma cells.