Multiepitope tissue analysis reveals SPPL3-mediated ADAM10 activation as a key step in the transformation of melanocytes

Ostalecki C, Lee JH, Dindorf J, Collenburg L, Schierer S, Simon B, Schliep S, Kremmer E, Schuler G, Baur A (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Science Signaling American Association for the Advancement of Science

Book Volume: 10

Journal Issue: 470

DOI: 10.1126/scisignal.aai8288

Abstract

The evolution of cancer is characterized by the appearance of specific mutations, but these mutations are translated into proteins that must cooperate to induce malignant transformation. Using a systemic approach with the multiepitope ligand cartography (MELC) technology, we analyzed protein expression profiles (PEPs) in nevi and BRAFV600E-positive superficial spreading melanomas (SSMs) from patient tissues to identify key transformation events. The PEPs in nevi and SSMs differed predominantly in the abundance of specific antigens, but the PEPs of nevi- and melanoma-associated keratinocytes gradually changed during the transformation process. A stepwise change in PEP with similar properties occurred in keratinocytes cocultured with melanoma cells. Analysis of the individual steps indicated that activation of the metalloproteinase ADAM10 by signal peptide peptidase-like 3 (SPPL3) triggered by mutant BRAFV600E was a critical transformation event. SPPL3-mediated ADAM10 activation involved the translocation of SPPL3 and ADAM10 into Rab4- or Rab27-positive endosomal compartments. This endosomal translocation, and hence ADAM10 activation, was inhibited by the presence of the tumor suppressor PTEN. Our findings suggest that systematic tissue antigen analysis could complement whole-genome approaches to provide more insight into cancer development.

Authors with CRIS profile

Gerold Schuler Lehrstuhl für Haut- und Geschlechtskrankheiten

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

Ostalecki, C., Lee, J.-H., Dindorf, J., Collenburg, L., Schierer, S., Simon, B.,... Baur, A. (2017). Multiepitope tissue analysis reveals SPPL3-mediated ADAM10 activation as a key step in the transformation of melanocytes. Science Signaling, 10(470). https://doi.org/10.1126/scisignal.aai8288

MLA:

Ostalecki, Christian, et al. "Multiepitope tissue analysis reveals SPPL3-mediated ADAM10 activation as a key step in the transformation of melanocytes." Science Signaling 10.470 (2017).

BibTeX: Download