{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FNDC1, a protein containing a fibronectin type III domain, has emerged as a multifunctional regulator in diverse biological processes. In several cancers—including prostate, gastric, breast, colorectal, and oral squamous cell carcinoma—overexpression of FNDC1 is associated with enhanced cell proliferation, migration, invasion, and resistance to therapy. In prostate cancer, for instance, FNDC1 is directly targeted by microRNA‐1207–3p, with its elevated expression correlating with aggressive tumor behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, multiple studies in gastric and breast cancers have demonstrated that increased FNDC1 levels portend poor clinical outcomes; in gastric cancer, FNDC1 not only serves as a prognostic biomarker but also appears to promote epithelial–mesenchymal transition via activation of the Wnt/β‐catenin signaling pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", while in breast cancer, elevated FNDC1 expression supports tumor cell proliferation and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In colorectal cancer, FNDC1 overexpression has been shown to enhance cell survival following chemoradiation by activating the PI3K/Akt pathway, thereby contributing to treatment resistance and a stem cell–like phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, genetic variants in FNDC1 have been linked to complications in Kawasaki disease, where specific polymorphisms correlate with an increased risk of coronary artery aneurysm formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in cancer, FNDC1 is implicated in non‐malignant processes. In the nematode Caenorhabditis elegans, the FNDC1 ortholog functions as a mitophagy receptor essential for the selective elimination of paternal mitochondria following fertilization, highlighting its importance in mitochondrial quality control during early embryogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Additionally, altered expression of FNDC1 has been observed in extracellular matrix remodeling: in degenerative intervertebral discs, its downregulation suggests a role in maintaining matrix homeostasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and in the vascular system, FNDC1 levels are modulated by lipid‐lowering interventions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, studies in bone biology indicate that FNDC1 may influence osteoblast proliferation and bone metabolism; suppression of FNDC1 is associated with reduced cell growth in osteoblasts"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and downregulation of FNDC1 by rutin treatment promotes autophagy, thereby ameliorating trabecular bone loss in osteoporosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, FNDC1 plays multifaceted roles as a promoter of oncogenic signaling and as a mediator of key physiological processes—including mitochondrial quality control and extracellular matrix regulation. Its involvement in activating pathways such as PI3K/Akt and Wnt/β‐catenin underscores its potential as both a prognostic biomarker and a therapeutic target in cancer and other diseases, while its diverse cellular functions may have broader implications for tissue homeostasis and regeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dibash K Das, Michelle Naidoo, Adeodat Ilboudo, et al. 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