@article{526835cd669f480298649a81969f61d5,
title = "Reciprocal Regulation of BRN2 and NOTCH1/2 Signaling Synergistically Drives Melanoma Cell Migration and Invasion",
abstract = "Phenotypic plasticity drives cancer progression, impacts treatment response, and is a major driver of therapeutic resistance. In melanoma, a regulatory axis between the MITF and BRN2 transcription factors has been reported to promote tumor heterogeneity by mediating switching between proliferative and invasive phenotypes, respectively. Despite strong evidence that subpopulations of cells that exhibit a BRN2high/MITFlow expression profile switch to a predominantly invasive phenotype, the mechanisms by which this switch is propagated and promotes invasion remain poorly defined. We have found that a reciprocal relationship between BRN2 and NOTCH1/2 signaling exists in melanoma cells in vitro, within patient datasets, and in in vivo primary and metastatic human tumors that bolsters acquisition of invasiveness. Working through the epigenetic modulator EZH2, the BRN2‒NOTCH1/2 axis is potentially a key mechanism by which the invasive phenotype is maintained. Given the emergence of agents targeting both EZH2 and NOTCH, understanding the mechanism through which BRN2 promotes heterogeneity may provide crucial biomarkers to predict treatment response to prevent metastasis.",
author = "Fane, {Mitchell E.} and Yash Chhabra and Loredana Spoerri and Simmons, {Jacinta L.} and Raquelle Ludwig and Elise Bonvin and Goding, {Colin R.} and Sturm, {Richard A.} and Boyle, {Glen M.} and Haass, {Nikolas K.} and Michael Piper and Smith, {Aaron G.}",
note = "Funding Information: This work was supported by funding from the Cancer Council of Queensland, APP1004663, and the National Health and Medical Research Council of Australia project grants APP1083612 and APP1022308. MEF was supported by an Australian Post-Graduate Research Award. NKH's contribution was supported by the National Health and Medical Research Council of Australia project grant APP1084893. The authors wish to gratefully acknowledge the support and assistance of Professor Ashani Weeraratna, Johns Hopkins School of Medicine, MD, USA, toward the completion of this manuscript. Conceptualization: MEF, AGS; Funding Acquisition: AGS, RAS, NKH, GMB; Investigation: MEF, YC, LS, JLS, RL, EB, AGS; Project Administration: MEF, AGS; Resources: CRG, RAS, GMB; Supervision: AGS, NKH, RAS; Writing - Original Draft Preparation: MEF, AGS; Writing - Review and Editing: MEF, YC, LS, JLS, RL, EB, CRG, RAS, GMB, NKH, MP, AGS Funding Information: This work was supported by funding from the Cancer Council of Queensland, APP1004663, and the National Health and Medical Research Council of Australia project grants APP1083612 and APP1022308. MEF was supported by an Australian Post-Graduate Research Award. NKH{\textquoteright}s contribution was supported by the National Health and Medical Research Council of Australia project grant APP1084893. The authors wish to gratefully acknowledge the support and assistance of Professor Ashani Weeraratna, Johns Hopkins School of Medicine, MD, USA, toward the completion of this manuscript. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2022",
month = jul,
doi = "10.1016/j.jid.2020.12.039",
language = "English (US)",
volume = "142",
pages = "1845--1857",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "7",
}