{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HOXC10, a member of the homeobox gene family, functions as a multifaceted transcription factor with critical roles in both embryonic development and cancer. During development, HOXC10 (and related Hox10 paralogs) contributes to axial patterning, limb morphogenesis, and the specification of motor neuron subtypes. Its regulated expression is essential for proper hindlimb identity, chondrogenesis, and osteogenesis, with alterations leading to vertebral transformations, limb malformations, and neuromuscular defects (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " In addition, HOXC10 protein levels are dynamically controlled during the cell cycle through APC‐mediated proteolysis, ensuring correct mitotic progression, as failure to degrade HOXC10 leads to metaphase arrest."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, aberrant regulation of HOXC10 has emerged as an important contributor to tumorigenesis and progression. Elevated HOXC10 expression is associated with enhanced invasiveness and metastatic behavior in cervical cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", as well as in malignancies of the gastro‐intestinal tract, thyroid, lung, and brain. In gastric cancer, for instance, HOXC10 overexpression, driven by epigenetic hypomethylation, promotes cell proliferation, migration and directly activates downstream target genes that fuel oncogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Similarly, in thyroid cancer and non‐small cell lung cancer, HOXC10 levels correlate with advanced clinical features and poor prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In glioma, HOXC10 upregulation further promotes an aggressive, immunosuppressive phenotype by directly binding to promoters of key regulatory genes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", whereas in breast cancer, its dynamic regulation appears to be involved in the cellular response to endocrine therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, HOXC10 activity can be modulated by noncoding RNAs in the tumor microenvironment. For example, in the bone marrow stroma of multiple myeloma patients, the long noncoding RNA HOXC‐AS3 interacts with and stabilizes HOXC10, thereby contributing to impaired osteogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Finally, altered HOXC10 expression in adipose tissue is correlated with regional fat distribution and obesity‐related traits, suggesting that this developmental regulator also influences adult metabolic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings reveal that HOXC10 is a pivotal transcriptional regulator whose precise expression is necessary for normal embryonic patterning and tissue differentiation, while its dysregulation contributes to tumor progression and metabolic dysfunction. Its diverse roles in both developmental processes and cancer-related pathways make HOXC10 a promising diagnostic marker and potential therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Olov Andersson, Eva Reissmann, Carlos F Ibáñez "}, {"type": "b", "children": [{"type": "t", "text": "Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.embor.7400752"}], "href": "https://doi.org/10.1038/sj.embor.7400752"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16845371"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16845371"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "April DeLaurier, Ronen Schweitzer, Malcolm Logan "}, {"type": "b", "children": [{"type": "t", "text": "Pitx1 determines the morphology of muscle, tendon, and bones of the hindlimb."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ydbio.2006.06.055"}], "href": "https://doi.org/10.1016/j.ydbio.2006.06.055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16989801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16989801"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anne M Boulet, Mario R Capecchi "}, {"type": "b", "children": [{"type": "t", "text": "Multiple roles of Hoxa11 and Hoxd11 in the formation of the mammalian forelimb zeugopod."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.00936"}], "href": "https://doi.org/10.1242/dev.00936"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14668414"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14668414"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yuanyuan Wu, Guoying Wang, Sheryl A Scott, et al. 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