{"entity": "publication", "iuid": "631eff0ff90346d7a156331ac7e2e608", "timestamp": "2026-08-20T22:16:50.061Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/631eff0ff90346d7a156331ac7e2e608.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/631eff0ff90346d7a156331ac7e2e608"}}, "title": "JNK-Dependent cJun Phosphorylation Mitigates TGF\u03b2- and EGF-Induced Pre-Malignant Breast Cancer Cell Invasion by Suppressing AP-1-Mediated Transcriptional Responses.", "authors": [{"family": "Sundqvist", "given": "Anders", "initials": "A"}, {"family": "Voytyuk", "given": "Oleksandr", "initials": "O"}, {"family": "Hamdi", "given": "Mohamed", "initials": "M"}, {"family": "Popeijus", "given": "Herman E", "initials": "HE"}, {"family": "van der Burgt", "given": "Corina Bijlsma-", "initials": "CB"}, {"family": "Janssen", "given": "Josephine", "initials": "J"}, {"family": "Martens", "given": "John W M", "initials": "JWM"}, {"family": "Moustakas", "given": "Aristidis", "initials": "A"}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH"}, {"family": "Ten Dijke", "given": "Peter", "initials": "P"}, {"family": "van Dam", "given": "Hans", "initials": "H"}], "type": "journal article", "published": "2019-11-21", "journal": {"title": "Cells", "issn": "2073-4409", "volume": "8", "issue": "12", "issn-l": "2073-4409"}, "abstract": "Transforming growth factor-\u03b2 (TGF\u03b2) has both tumor-suppressive and tumor-promoting effects in breast cancer. These functions are partly mediated through Smads, intracellular transcriptional effectors of TGF\u03b2. Smads form complexes with other DNA-binding transcription factors to elicit cell-type-dependent responses. Previously, we found that the collagen invasion and migration of pre-malignant breast cancer cells in response to TGF\u03b2 and epidermal growth factor (EGF) critically depend on multiple Jun and Fos components of the activator protein (AP)-1 transcription factor complex. Here we report that the same process is negatively regulated by Jun N-terminal kinase (JNK)-dependent cJun phosphorylation. This was demonstrated by analysis of phospho-deficient, phospho-mimicking, and dimer-specific cJun mutants, and experiments employing a mutant version of the phosphatase MKP1 that specifically inhibits JNK. Hyper-phosphorylation of cJun by JNK strongly inhibited its ability to induce several Jun/Fos-regulated genes and to promote migration and invasion. These results show that MEK-AP-1 and JNK-phospho-cJun exhibit distinct pro- and anti-invasive functions, respectively, through differential regulation of Smad- and AP-1-dependent TGF\u03b2 target genes. Our findings are of importance for personalized cancer therapy, such as for patients suffering from specific types of breast tumors with activated EGF receptor-Ras or inactivated JNK pathways.", "doi": "10.3390/cells8121481", "pmid": "31766464", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6952832"}, {"db": "pii", "key": "cells8121481"}], "notes": [], "created": "2026-08-20T13:40:18.947Z", "modified": "2026-08-20T13:40:18.984Z"}