AG Bosserhoff (Chair 1)
Chair of Biochemistry and Molecular Medicine
Research focus: Melanoma
There is also evidence that MIA has regulating effects on other proteins. For this reason we examine the regulation of p54nrb by MIA and the role played by this protein in the development, progression and metastasis of melanoma.
Our data further demonstrated that loss of the tumor suppressor protein E-cadherin activates signaling cascades leading to development and progression of melanoma. It leads to a constitutive activity of the transcription factor NFkappaB which has N-cadherin as direct target gene.
Furthermore, the proto-oncogene c-Jun, part of the transcription factor family AP-1, is hyper-activated in melanoma. We showed a link between loss of E-cadherin expression and transcriptional activity of c-Jun. Besides the possible regulation of c-Jun by the common signaling pathways JNK/ERK, we identified a novel E-cadherin dependent signaling cascade resulting in c-Jun activation in malignant melanoma.
Moreover, we detected one microRNA, the miR-125b, directly regulating the transcription factor c-Jun at the posttranscriptional level. Further investigations of our group aim to identifiy the functional role of the cytoskeletal network on the regulation of c-Jun.
Due to the pleiotropic effects of miRNAs on global gene expression, this class of molecules is also considered to play a central role in the formation and progression of presumably all kinds of human tumors. However, their impact on melanomagenesis in particular remains only rudimentary understood.
In addition to the function of mature miRNAs as key post-transcriptional regulatory elements, their processing and characterization in melanoma is the focus of our current research.
Recently, we were able to show an increase of BMP7 expression in melanoma compared to benign nevi and thereby determine BMP7 as a potential novel prognostic marker for melanoma progression.
In further studies we aim to identify and characterize new BMP target genes implicated in melanoma formation and progression.
Putative further effects of the loss of MTAP and the accumulation of MTA are still largely unexplored. In order to better understand the consequences of this loss of expression, the regulatory function of MTAP is also examined in more detail.
Further, in several co-operations we determine the potential use of MIA as a marker or in therapy for osteoarthritis or other kinds of cartilage diseases.