C-Jun drives melanoma progression in PTEN wild type melanoma cells

Kappelmann-Fenzl M, Gebhard C, Matthies AO, Kuphal S, Rehli M, Boßerhoff AK (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Cell Death & Disease Nature Publishing Group: Open Access Journals - Option B / Nature Publishing Group

Book Volume: 10

Article Number: 584

Journal Issue: 8

DOI: 10.1038/s41419-019-1821-9

Abstract

Due to the critical impact of active AP-1 transcription factors in melanoma, it is important to define their target genes and to identify and ultimately inhibit oncogenic signals. Here we mapped the genome-wide occupancy of the AP-1 family member c-Jun in different melanoma cells and correlated AP-1 binding with transcriptome data to detect genes in melanoma regulated by c-Jun. Our analysis shows that c-Jun supports the malignant phenotype by deregulating genes in cancer-relevant signaling pathways, such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K) pathways. Moreover, we demonstrate that the importance of c-Jun depends on melanoma stage and mutation status of the tumor suppressor PTEN. Our study reveals that activation of c-Jun overrules the tumor suppressive effect of PTEN in early melanoma development. These findings help to understand the relevance of c-Jun within cancer pathways in different melanoma cell types, especially in relation to MAPK and PI3K pathways, which are commonly deregulated in melanomas. Consequently, targeting c-Jun in PTEN+ melanoma cells may represent a promising therapeutic strategy to inhibit survival of melanoma cells to prevent the development of a metastatic phenotype.

Authors with CRIS profile

Melanie Kappelmann-Fenzl Lehrstuhl für Biochemie und Molekulare Medizin Alexander Oliver Matthies Lehrstuhl für Biochemie und Molekulare Medizin Silke Kuphal Lehrstuhl für Biochemie und Molekulare Medizin Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE)

How to cite

APA:

Kappelmann-Fenzl, M., Gebhard, C., Matthies, A.O., Kuphal, S., Rehli, M., & Boßerhoff, A.K. (2019). C-Jun drives melanoma progression in PTEN wild type melanoma cells. Cell Death & Disease, 10(8). https://dx.doi.org/10.1038/s41419-019-1821-9

MLA:

Kappelmann-Fenzl, Melanie, et al. "C-Jun drives melanoma progression in PTEN wild type melanoma cells." Cell Death & Disease 10.8 (2019).

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