{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FOCAD is emerging as a multifunctional protein with diverse roles in cell adhesion, tumor suppression, cell‐cycle regulation, ferroptosis, and even mRNA surveillance. In non–small cell lung cancer, FOCAD transcription is negatively regulated by NRF2 through a complex involving RPA1 and antioxidant response elements, and its expression promotes focal adhesion kinase (FAK) activity. This in turn enhances the sensitivity of cancer cells to cysteine deprivation–induced ferroptosis by driving mitochondrial metabolism and tricarboxylic acid cycle activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In gliomas, FOCAD (also known as focadhesin, encoded by KIAA1797) localizes to focal adhesions by interacting with proteins such as vinculin. Its restoration in glioma cells reduces colony formation, migration, and invasion, while its loss is associated with enhanced microtubule assembly, accelerated G2/M progression, and ultimately worse patient survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Germline deletions and predicted deleterious variants in FOCAD have been identified in patients with familial polyposis and colorectal cancer, suggesting that its monoallelic loss confers a moderate predisposition to tumorigenesis in the colon."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, regulatory studies indicate that genetic variation in other loci (e.g., HACD4) can modulate FOCAD mRNA levels in human carotid plaques, and network analyses show that FOCAD expression in the heart is correlated with protein biosynthetic processes in the lung—hinting at a role in inter‐tissue signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, proteomic investigations into RNA decay pathways revealed that FOCAD interacts with the cytoplasmic exoribonuclease cofactor SKIV2L, suggesting its involvement in translation surveillance and mRNA turnover."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, in triple negative breast cancer, a FOCAD/miR‑491‑5p axis was found to exert tumor suppressor functions that are associated with improved overall survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies demonstrate that FOCAD plays multifaceted roles—regulating cell–matrix adhesion, cell–cycle progression, ferroptosis, and even aspects of mRNA decay and inter–tissue communication. The broad impact of FOCAD on tumor biology across several cancer types underscores its promise both as a therapeutic target and as a genetic predisposition marker.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pengfei Liu, Di Wu, Jinyue Duan, et al. 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