PuSH - Publikationsserver des Helmholtz Zentrums München

Ostalecki, C.* ; Lee, J.H.* ; Dindorf, J.* ; Collenburg, L.* ; Schierer, S.* ; Simon, B.* ; Schliep, S.* ; Kremmer, E. ; Schuler, G.* ; Baur, A.S.*

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

Sci. Signal. 10:eaai8288 (2017)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 BRAF(V600E)-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 BRAF(V600E) 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.
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 1945-0877
e-ISSN 1937-9145
Zeitschrift Science Signaling
Quellenangaben Band: 10, Heft: 470, Seiten: , Artikelnummer: eaai8288 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed