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E-GEOD-69403 - Interactions of melanoma cells with distal keratinocytes trigger metastasis via Notch signaling inhibition of MITF

Status
Released on 30 July 2015, last updated on 19 August 2015
Organism
Homo sapiens
Samples (4)
Protocols (4)
Description
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 introduce a novel perspective, suggesting 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 novel prevention opportunities via targeting specific microenvironment. Two replicates of Notch-activated cells that were seeded on Delta-like-1 (DLL1) (2 ng/µl ) coated plates were compared to two replicates of cells without Notch activation. The goal of this experiment is to evaluate the changes of miRs expression in melanoma cells upon Notch signaling activation.
Experiment type
RNA-seq of non coding RNA 
Contacts
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-69403.idf.txt
Sample and data relationshipE-GEOD-69403.sdrf.txt
Processed data (1)E-GEOD-69403.processed.1.zip
Additional data (1)E-GEOD-69403.additional.1.zip
Links