{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough SPDYE18 is not explicitly mentioned in the provided abstracts, studies on functionally related immediate early response genes—particularly IER2—offer insights that may extend to SPDYE18. In one study, increased expression of IER2 was shown to drive tumor cell motility and invasiveness. Its accumulation in the nucleus upon relief of contact inhibition appears to promote metastatic progression, as ectopic IER2 expression enhances cell migration, invasiveness, and ultimately metastasis formation in tumor models. This also correlated with poor patient outcomes in several tumor types."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "In another investigation focusing on melanoma, sustained IER2 expression was found to induce senescence in a subset of tumor cells via a p53/MAPK/AKT-dependent pathway. The senescent cells adopted a distinctive secretory profile marked by high osteopontin levels. Notably, nuclear localization of IER2 was critical for this process, and the resulting osteopontin secretion stimulated the migration and invasion of adjacent non-senescent melanoma cells. This work underscores a dual function whereby an immediate early gene can modulate both cell cycle arrest and paracrine signals to promote tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "A third study, while not examining IER2 directly, identified a novel gene (pip92) that is robustly upregulated following cerebral ischemia, promoting apoptotic cell death in primary neurons. The discovery of such differentially regulated genes after ischemia hints at overarching cellular stress-response pathways that may be shared with immediate early response genes like IER2 and, by extension, could be informative in understanding SPDYE18’s potential roles under stress or injury conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A Neeb, S Wallbaum, N Novac, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The immediate early gene Ier2 promotes tumor cell motility and metastasis, and predicts poor survival of colorectal cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.535"}], "href": "https://doi.org/10.1038/onc.2011.535"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22120713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22120713"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lenka Kyjacova, Rafael Saup, Kerstin Rönsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IER2-induced senescence drives melanoma invasion through osteopontin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-021-02027-6"}], "href": "https://doi.org/10.1038/s41388-021-02027-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34611309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34611309"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Armin Schneider, Achim Fischer, Daniela Weber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Restriction-mediated differential display (RMDD) identifies pip92 as a pro-apoptotic gene product induced during focal cerebral ischemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cereb Blood Flow Metab (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/01.WCB.0000104960.26014.7A"}], "href": "https://doi.org/10.1097/01.WCB.0000104960.26014.7A"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14747749"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14747749"}]}]}]}