{"entity": "publication", "iuid": "99728378ffeb403da7f5e071a3dd85d1", "timestamp": "2026-08-26T22:46:44.499Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/99728378ffeb403da7f5e071a3dd85d1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/99728378ffeb403da7f5e071a3dd85d1"}}, "title": "Serglycin activates pro-tumorigenic signaling and controls glioblastoma cell stemness, differentiation and invasive potential.", "authors": [{"family": "Manou", "given": "Dimitra", "initials": "D"}, {"family": "Bouris", "given": "Panagiotis", "initials": "P"}, {"family": "Kletsas", "given": "Dimitris", "initials": "D"}, {"family": "G\u00f6tte", "given": "Martin", "initials": "M"}, {"family": "Greve", "given": "Burkhard", "initials": "B"}, {"family": "Moustakas", "given": "Aristidis", "initials": "A"}, {"family": "Karamanos", "given": "Nikos K", "initials": "NK"}, {"family": "Theocharis", "given": "Achilleas D", "initials": "AD"}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Matrix Biol Plus", "issn": "2590-0285", "volume": "6-7", "pages": "100033", "issn-l": null}, "abstract": "Despite the functional role of serglycin as an intracellular proteoglycan, a variety of malignant cells depends on its expression and constitutive secretion to advance their aggressive behavior. Serglycin arose to be a biomarker for glioblastoma, which is the deadliest and most treatment-resistant form of brain tumor, but its role in this disease is not fully elucidated. In our study we suppressed the endogenous levels of serglycin in LN-18 glioblastoma cells to decipher its involvement in their malignant phenotype. Serglycin suppressed LN-18 (LN-18shSRGN) glioblastoma cells underwent astrocytic differentiation characterized by induced expression of GFAP, SPARCL-1 and SNAIL, with simultaneous loss of their stemness capacity. In particular, LN-18shSRGN cells presented decreased expression of glioma stem cell-related genes and ALDH1 activity, accompanied by reduced colony formation ability. Moreover, the suppression of serglycin in LN-18shSRGN cells retarded the proliferative and migratory rate, the invasive potential in vitro and the tumor burden in vivo. The lack of serglycin in LN-18shSRGN cells was followed by G2 arrest, with subsequent reduction of the expression of cell-cycle regulators. LN-18shSRGN cells also exhibited impaired expression and activity of proteolytic enzymes such as MMPs, TIMPs and uPA, both in vitro and in vivo. Moreover, suppression of serglycin in LN-18shSRGN cells eliminated the activation of pro-tumorigenic signal transduction. Of note, LN-18shSRGN cells displayed lower expression and secretion levels of IL-6, IL-8 and CXCR-2. Concomitant, serglycin suppressed LN-18shSRGN cells demonstrated repressed phosphorylation of ERK1/2, p38, SRC and STAT-3, which together with PI3K/AKT and IL-8/CXCR-2 signaling control LN-18 glioblastoma cell aggressiveness. Collectively, the absence of serglycin favors an astrocytic fate switch and a less aggressive phenotype, characterized by loss of pluripotency, block of the cell cycle, reduced ability for ECM proteolysis and pro-tumorigenic signaling attenuation.", "doi": "10.1016/j.mbplus.2020.100033", "pmid": "33543029", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7852318"}, {"db": "pii", "key": "S2590-0285(20)30014-4"}], "notes": [], "created": "2026-08-20T08:00:38.589Z", "modified": "2026-08-20T08:00:38.654Z"}