“…Additionally, MITF activity does not simply correlate with expression levels but also correlates with cell background, which dictates MITF protein stability [ 168 ], subcellular localization [ 169 ], protein interactors [ 170 , 171 ], microRNA regulation [ 172 , 173 , 174 , 175 ], DNA binding affinity [ 176 ], and DNA accessibility [ 64 ]. Furthermore, MITF activity depends on tumor microenvironment (TME) conditions, such as nutrient depletion [ 177 , 178 ], immune surveillance and inflammation [ 179 , 180 , 181 ], heterotypic interactions with normal cells [ 182 ], hypoxia [ 183 , 184 ], extracellular matrix (ECM) composition [ 185 ], and drug treatment [ 111 , 180 , 186 , 187 ]. Hence, an integrative adaptive response tuning MITF activity alters a cell’s probability of adopting a particular phenotypic state [ 167 , 188 ].…”