NFIB mediates BRN2 driven melanoma cell migration and invasion through regulation of EZH2 and MITF

Fane, Mitchell E., Chhabra, Yash, Hollingsworth, David E. J., Simmons, Jacinta L., Spoerri, Loredana, Oh, Tae Gyu, Chauhan, Jagat, Chin, Toby, Harris, Lachlan, Harvey, Tracey J., Muscat, George E. O., Goding, Colin R., Sturm, Richard A., Haass, Nikolas K., Boyle, Glen M., Piper, Michael and Smith, Aaron G. (2017) NFIB mediates BRN2 driven melanoma cell migration and invasion through regulation of EZH2 and MITF. EBioMedicine, 16 63-75. doi:10.1016/j.ebiom.2017.01.013

Author Fane, Mitchell E.
Chhabra, Yash
Hollingsworth, David E. J.
Simmons, Jacinta L.
Spoerri, Loredana
Oh, Tae Gyu
Chauhan, Jagat
Chin, Toby
Harris, Lachlan
Harvey, Tracey J.
Muscat, George E. O.
Goding, Colin R.
Sturm, Richard A.
Haass, Nikolas K.
Boyle, Glen M.
Piper, Michael
Smith, Aaron G.
Title NFIB mediates BRN2 driven melanoma cell migration and invasion through regulation of EZH2 and MITF
Journal name EBioMedicine   Check publisher's open access policy
ISSN 2352-3964
Publication date 2017-01-16
Year available 2017
Sub-type Article (original research)
DOI 10.1016/j.ebiom.2017.01.013
Open Access Status DOI
Volume 16
Start page 63
End page 75
Total pages 13
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Abstract While invasion and metastasis of tumour cells are the principle factor responsible for cancer related deaths, the mechanisms governing the process remain poorly defined. Moreover, phenotypic divergence of sub-populations of tumour cells is known to underpin alternative behaviors linked to tumour progression such as proliferation, survival and invasion. In the context of melanoma, heterogeneity between two transcription factors, BRN2 and MITF, has been associated with phenotypic switching between predominantly invasive and proliferative behaviors respectively. Epigenetic changes, in response to external cues, have been proposed to underpin this process, however the mechanism by which the phenotypic switch occurs is unclear. Here we report the identification of the NFIB transcription factor as a novel downstream effector of BRN2 function in melanoma cells linked to the migratory and invasive characteristics of these cells. Furthermore, the function of NFIB appears to drive an invasive phenotype through an epigenetic mechanism achieved via the upregulation of the polycomb group protein EZH2. A notable target of NFIB mediated up-regulation of EZH2 is decreased MITF expression, which further promotes a less proliferative, more invasive phenotype. Together our data reveal that NFIB has the ability to promote dynamic changes in the chromatin state of melanoma cells to facilitate migration, invasion and metastasis.
Keyword BRN2
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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