An interesting axis of communication has been identified between melanoma cells and keratinocytes of the epidermal layer: when tumor cells come in contact with keratinocytes, Notch pathway activation impairs Microphthalmia-associated transcription factor (MITF) binding and repression of the miR-222/221 promoter, and consequently promotes tumor invasion putatively through GRB10 or ESR1 inhibition [37]. Here, ESR1 is linked to neoplasm.