@article {3132768,
	title = {Interactions of Melanoma Cells with Distal Keratinocytes Trigger Metastasis via Notch Signaling Inhibition of MITF},
	journal = {Mol Cell},
	volume = {59},
	number = {4},
	year = {2015},
	note = {Golan, TamarMesser, Arielle RAmitai-Lange, AyaMelamed, Ze{\textquoteright}evOhana, ReutBell, Rachel EKapitansky, OxanaLerman, GalyaGreenberger, ShoshanaKhaled, MehdiAmar, NiraAlbrengues, JeanGaggioli, CedricGonen, PinchasTabach, YuvalSprinzak, DavidShalom-Feuerstein, RubyLevy, CarmitengResearch Support, Non-U.S. Gov{\textquoteright}tMol Cell. 2015 Aug 20;59(4):664-76. doi: 10.1016/j.molcel.2015.06.028. Epub 2015 Jul 30.},
	month = {Aug 20},
	pages = {664-76},
	edition = {2015/08/04},
	abstract = {The most critical stage in initiation of melanoma metastasis is the radial to vertical growth transition, yet the triggers of this transition remain elusive. We suggest that the microenvironment drives melanoma metastasis independently of mutation acquisition. Here we examined the changes in microenvironment that occur during melanoma radial growth. We show that direct contact of melanoma cells with the remote epidermal layer triggers vertical invasion via Notch signaling activation, the latter serving to inhibit MITF function. Briefly, within the native Notch ligand-free microenvironment, MITF, the melanocyte lineage master regulator, binds and represses miR-222/221 promoter in an RBPJK-dependent manner. However, when radial growth brings melanoma cells into contact with distal differentiated keratinocytes that express Notch ligands, the activated Notch intracellular domain impairs MITF binding to miR-222/221 promoter. This de-repression of miR-222/221 expression triggers initiation of invasion. Our findings may direct melanoma prevention opportunities via targeting specific microenvironments.},
	keywords = {Animals, Base Sequence, Binding Sites, Cell Communication, Cell Line, Tumor, Coculture Techniques, Gene Expression Regulation, Neoplastic, Keratinocytes/*physiology, Melanoma, Experimental/metabolism/*secondary, Mice, Inbred NOD, Mice, SCID, Microphthalmia-Associated Transcription Factor/*metabolism, MicroRNAs/genetics/metabolism, Neoplasm Invasiveness, Neoplasm Transplantation, Promoter Regions, Genetic, Receptors, Notch/metabolism, RNA Interference, Signal Transduction, Skin Neoplasms/metabolism/*pathology},
	isbn = {1097-4164 (Electronic)1097-2765 (Linking)},
	author = {Golan, T. and Messer, A. R. and Amitai-Lange, A. and Melamed, Z. and Ohana, R. and Bell, R. E. and Kapitansky, O. and Lerman, G. and Greenberger, S. and Khaled, M. and Amar, N. and Albrengues, J. and Gaggioli, C. and Gonen, P. and Tabach, Y. and Sprinzak, D. and Shalom-Feuerstein, R. and Levy, C.}
}
