{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FILIP1L (Filamin A‐Interacting Protein 1‐Like) is emerging as a multifunctional protein that influences diverse cellular processes through context‐dependent mechanisms. In several tumor models—including ovarian, colorectal, and glioblastoma—FILIP1L acts as a tumor suppressor by inhibiting cell migration, invasion, and angiogenesis. Its anti‐invasive activity is mediated, in part, by transcriptional downregulation of matrix metalloproteinases (MMP3, MMP7, and MMP9) and by suppressing the canonical WNT signaling pathway through the enhancement of β‐catenin degradation. Consequently, epigenetic silencing of FILIP1L (via promoter hypermethylation) has been associated with a more invasive phenotype, chemoresistance, and poorer prognosis in cancer patients."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in tumor suppression, FILIP1L has been implicated in other physiological and pathophysiological processes. Genetic studies have linked variants in the FILIP1L locus with developmental anomalies such as nonsyndromic cleft lip with or without cleft palate."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, a circular RNA derived from the FILIP1L transcript is upregulated in spinal neurons during chronic inflammatory pain, and modulation of this circRNA alters nociceptive thresholds, suggesting that FILIP1L may also contribute to the regulation of neuropathic pain."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n FILIP1L has further been shown to participate in cellular stress responses. For example, it interacts with heat shock factor 1 (Hsf1) and promotes its ubiquitination and proteasome‐mediated degradation, thereby modulating the heat shock response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Additionally, induction of FILIP1L by topoisomerase II poisons such as doxorubicin is required for apoptosis in cancer cells, pointing to its potential role in the efficacy of chemotherapeutic regimens."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, accumulated evidence indicates that FILIP1L is a key regulatory protein that suppresses metastasis through inhibition of the canonical WNT/β‐catenin pathway and downregulation of MMPs, while also modulating stress responses and apoptosis. Its downregulation—often through epigenetic mechanisms—correlates with enhanced tumor aggressiveness, chemoresistance, and developmental defects, thereby making it an attractive prognostic marker and potential therapeutic target in cancer and other diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mijung Kwon, Soo Jin Lee, Yarong Wang, et al. 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