{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DEPP1, also known as decidual protein induced by progesterone (or C10orf10), is a multifunctional protein whose expression is modulated by diverse stress, hormonal, and metabolic signals and whose activity appears to influence cell survival and differentiation in several tissues. In neuroblastoma cells, for example, DEPP1 is a direct transcriptional target of FOXO3; it localizes to both peroxisomes and mitochondria, where its upregulation impairs reactive oxygen species (ROS) detoxification—by reducing catalase activity—and sensitizes cells to ROS‐induced apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the reproductive system, DEPP1 is rapidly induced in human endometrial stromal cells in response to progesterone and androgens, leading to activation of signaling pathways (including the MAPK/Elk-1 axis) that are likely critical for decidualization and placental development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Its regulation extends to the vascular compartment as well, where FOXO-dependent induction in endothelial cells under hypoxic conditions suggests a role in modulating vascular stress responses and possibly angiogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In metabolic tissues, DEPP1 expression is also finely tuned: in white adipose tissue, its levels increase during fasting and decrease upon insulin stimulation, implicating DEPP1 in the regulation of glucose and lipid metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, hepatic overexpression of DEPP1 leads to ROS accumulation that, in turn, elevates fibroblast growth factor 21 (FGF21) expression—promoting fatty acid oxidation and ketogenesis while suppressing lipogenesis and gluconeogenesis—thereby contributing to improved metabolic homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additional studies have linked DEPP1 to the regulation of autophagy; in chondrocytes, for instance, DEPP1 appears to facilitate mitochondrial autophagic functions, with reduced expression correlating with osteoarthritic changes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Clinically, lower DEPP1 (C10orf10) expression in breast cancer tissues is associated with poorer patient survival, underscoring its potential value as a prognostic biomarker, whereas in glioma cells, hypoxia-induced upregulation of DEPP1 may contribute to tumor vascularization and progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that DEPP1 functions as a stress‐responsive regulator, integrating hormonal, metabolic, and oxidative cues to modulate key cellular processes such as apoptosis, autophagy, angiogenesis, and energy metabolism across diverse tissues.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stefan Salcher, Judith Hagenbuchner, Kathrin Geiger, et al. 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