{"entity": "publication", "iuid": "4c24079e980f4d5a92a0cefe7b18f5ef", "timestamp": "2026-03-10T02:56:13.593Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4c24079e980f4d5a92a0cefe7b18f5ef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4c24079e980f4d5a92a0cefe7b18f5ef"}}, "title": "PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer.", "authors": [{"family": "Costa", "given": "T\u00e2nia D F", "initials": "TDF"}, {"family": "Zhuang", "given": "Ting", "initials": "T"}, {"family": "Lorent", "given": "Julie", "initials": "J"}, {"family": "Turco", "given": "Emilia", "initials": "E"}, {"family": "Olofsson", "given": "Helene", "initials": "H"}, {"family": "Masia-Balague", "given": "Miriam", "initials": "M"}, {"family": "Zhao", "given": "Miao", "initials": "M"}, {"family": "Rabieifar", "given": "Parisa", "initials": "P"}, {"family": "Robertson", "given": "Neil", "initials": "N"}, {"family": "Kuiper", "given": "Raoul", "initials": "R"}, {"family": "Sj\u00f6lund", "given": "Jonas", "initials": "J"}, {"family": "Spiess", "given": "Matthias", "initials": "M"}, {"family": "Hern\u00e1ndez-Varas", "given": "Pablo", "initials": "P"}, {"family": "Rabenhorst", "given": "Uta", "initials": "U"}, {"family": "Roswall", "given": "Pernilla", "initials": "P"}, {"family": "Ma", "given": "Ran", "initials": "R"}, {"family": "Gong", "given": "Xiaowei", "initials": "X"}, {"family": "Hartman", "given": "Johan", "initials": "J"}, {"family": "Pietras", "given": "Kristian", "initials": "K"}, {"family": "Adams", "given": "Peter D", "initials": "PD"}, {"family": "Defilippi", "given": "Paola", "initials": "P"}, {"family": "Str\u00f6mblad", "given": "Staffan", "initials": "S"}], "type": "journal article", "published": "2019-08-09", "journal": {"volume": "10", "issn": "2041-1723", "issue": "1", "pages": "3589", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Overcoming cellular growth restriction, including the evasion of cellular senescence, is a hallmark of cancer. We report that PAK4 is overexpressed in all human breast cancer subtypes and associated with poor patient outcome. In mice, MMTV-PAK4 overexpression promotes spontaneous mammary cancer, while PAK4 gene depletion delays MMTV-PyMT driven tumors. Importantly, PAK4 prevents senescence-like growth arrest in breast cancer cells in vitro, in vivo and ex vivo, but is not needed in non-immortalized cells, while PAK4 overexpression in untransformed human mammary epithelial cells abrogates H-RAS-V12-induced senescence. Mechanistically, a PAK4 - RELB - C/EBP\u03b2 axis controls the senescence-like growth arrest and a PAK4 phosphorylation residue (RELB-Ser151) is critical for RELB-DNA interaction, transcriptional activity and expression of the senescence regulator C/EBP\u03b2. These findings establish PAK4 as a promoter of breast cancer that can overcome oncogene-induced senescence and reveal a selective vulnerability of cancer to PAK4 inhibition.", "doi": "10.1038/s41467-019-11510-4", "pmid": "31399573", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-11510-4"}, {"db": "pmc", "key": "PMC6689091"}], "notes": [], "created": "2019-12-02T16:53:04.441Z", "modified": "2020-01-21T13:56:15.526Z"}