{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSOX1 is a developmental transcription factor that plays a critical role in early embryogenesis and neural differentiation. In the lens, for example, deletion of Sox1 in mice disrupted the expression of gamma‐crystallin genes, leading to failure of lens fiber cell elongation and resulting in cataract formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In neural progenitors, overexpression of SOX1 is sufficient to promote neuronal lineage commitment by directly binding to the Hes1 promoter to suppress its transcription and by attenuating Wnt/β‐catenin signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, SOX1 is required for the proper fate determination of spinal interneurons, where its absence forces cells to switch lineages"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and its timely expression has been shown as pivotal in neural induction protocols from pluripotent and mesenchymal stem cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various cancers, SOX1 primarily functions as a tumor suppressor by interfering with oncogenic signaling pathways. In hepatocellular carcinoma, reduced SOX1 expression—often through promoter hypermethylation—leads to aberrant activation of Wnt/β‐catenin signals and enhanced tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Similarly, in cervical and breast cancers, restoration of SOX1 activity inhibits cell proliferation and invasion by suppressing key Wnt targets and related pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In laryngeal squamous cell carcinoma, overexpression of SOX1 not only dampens proliferative signals but also negatively regulates SOX2 expression and remodels actin cytoskeletal dynamics to reduce migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Furthermore, in esophageal squamous cell and nasopharyngeal carcinomas, low SOX1 levels are significantly associated with aggressive tumor behavior, while forced expression promotes cellular senescence and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In non‐small cell lung cancer, silencing of SOX1 via DNA methylation has been linked to increased autophagy and enhanced cisplatin resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical tumor‐suppressive functions, SOX1 has been implicated in sustaining cancer stem cell properties in certain contexts. In glioblastoma, elevated SOX1 expression in glioma stem cells is associated with increased self‐renewal and tumor initiation, highlighting a role in maintaining a stem-like, undifferentiated state."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " Additionally, within a distinct subtype of small‐cell lung cancer (SCLC-Aα), SOX1 collaborates with NKX2-1 via shared super-enhancers to preserve a neural/neuronal lineage identity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent analyses have further revealed that the activity of SOX1 is modulated by post-translational modifications. A novel motif within SOX1, potentially subject to phospho-sumoyl switching, may regulate its DNA binding and protein interaction capabilities, thereby finely tuning its transcriptional regulatory functions in both developmental and oncogenic settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOverall, SOX1 acts as a pivotal transcriptional regulator with diverse functions ranging from promoting neural differentiation and maintaining the undifferentiated status of progenitor cells to suppressing tumor growth and invasion by countering oncogenic signaling pathways. Its context-dependent roles, regulated through epigenetic mechanisms and post-translational modifications, underscore its importance in normal development and cancer pathogenesis.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S Nishiguchi, H Wood, H Kondoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sox1 directly regulates the gamma-crystallin genes and is essential for lens development in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (1998)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.12.6.776"}], "href": "https://doi.org/10.1101/gad.12.6.776"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9512512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9512512"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lixin Kan, Nipan Israsena, Zuoli Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sox1 acts through multiple independent pathways to promote neurogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ydbio.2004.02.005"}], "href": "https://doi.org/10.1016/j.ydbio.2004.02.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15110721"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15110721"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Helen Panayi, Elena Panayiotou, Michael Orford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sox1 is required for the specification of a novel p2-derived interneuron subtype in the mouse ventral spinal cord."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.2402-10.2010"}], "href": "https://doi.org/10.1523/JNEUROSCI.2402-10.2010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20844123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20844123"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "M Diana Neely, Michael J Litt, Andrew M Tidball, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DMH1, a highly selective small molecule BMP inhibitor promotes neurogenesis of hiPSCs: comparison of PAX6 and SOX1 expression during neural induction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "ACS Chem Neurosci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/cn300029t"}], "href": "https://doi.org/10.1021/cn300029t"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22860217"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22860217"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nianhua Feng, Qin Han, Jing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Generation of highly purified neural stem cells from human adipose-derived mesenchymal stem cells by Sox1 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells Dev (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/scd.2013.0263"}], "href": "https://doi.org/10.1089/scd.2013.0263"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24138016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24138016"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Julia Morys, Paulina Borkowska, Aleksandra Zielinska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Study of the influence of NGF-β gene overexpression in human mesenchymal stem cells on the expression level of SOX1 and neural pathway genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-022-07283-7"}], "href": "https://doi.org/10.1007/s11033-022-07283-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35348963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35348963"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Chun-Ming Tsao, Ming-De Yan, Yu-Lueng Shih, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOX1 functions as a tumor suppressor by antagonizing the WNT/β-catenin signaling pathway in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.25933"}], "href": "https://doi.org/10.1002/hep.25933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22767186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22767186"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jinshu Lou, Kai Zhang, Jing Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prognostic significance of SOX-1 expression in human hepatocelluar cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Clin Exp Pathol (2015)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26191244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26191244"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Ya-Wen Lin, Chun-Ming Tsao, Pei-Ning Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOX1 suppresses cell growth and invasion in cervical cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gynecol Oncol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygyno.2013.07.111"}], "href": "https://doi.org/10.1016/j.ygyno.2013.07.111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23927962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23927962"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Lingqin Song, Di Liu, Jianjun He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOX1 inhibits breast cancer cell growth and invasion through suppressing the Wnt/β-catenin signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "APMIS (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/apm.12543"}], "href": "https://doi.org/10.1111/apm.12543"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27206213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27206213"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Ning Yang, Yan Wang, Lian Hui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOX 1, contrary to SOX 2, suppresses proliferation, migration, and invasion in human laryngeal squamous cell carcinoma by inhibiting the Wnt/β-catenin pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-3389-z"}], "href": "https://doi.org/10.1007/s13277-015-3389-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26040764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26040764"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Abolfazl Rad, Saeed Esmaeili Dizghandi, Mohammad Reza Abbaszadegan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOX1 is correlated to stemness state regulator SALL4 through progression and invasiveness of esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2016.08.045"}], "href": "https://doi.org/10.1016/j.gene.2016.08.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27576349"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27576349"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Xin-Xing Lei, Yun Liu, Jin-Xing Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOX1 promotes differentiation of nasopharyngeal carcinoma cells by activating retinoid metabolic pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-2513-1"}], "href": "https://doi.org/10.1038/s41419-020-2513-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32382038"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32382038"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Ning Li, Xiaobing Li, Suyun Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cisplatin-induced downregulation of SOX1 increases drug resistance by activating autophagy in non-small cell lung cancer cell."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2013.08.065"}], "href": "https://doi.org/10.1016/j.bbrc.2013.08.065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23994634"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23994634"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Ning Li, Suyun Li "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic inactivation of SOX1 promotes cell migration in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-3107-x"}], "href": "https://doi.org/10.1007/s13277-015-3107-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25613070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25613070"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Idoia Garcia, Juncal Aldaregia, Jelena Marjanovic Vicentic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogenic activity of SOX1 in glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep46575"}], "href": "https://doi.org/10.1038/srep46575"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28425506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28425506"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Ranran Kong, Ayushi S Patel, Takashi Sato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional Circuitry of NKX2-1 and SOX1 Defines an Unrecognized Lineage Subtype of Small-Cell Lung Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Crit Care Med (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1164/rccm.202110-2358OC"}], "href": "https://doi.org/10.1164/rccm.202110-2358OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35848993"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35848993"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Azaz Ahmad, Stephanie Strohbuecker, Claudia Scotti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In Silico Identification of SOX1 Post-Translational Modifications Highlights a Shared Protein Motif."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells9112471"}], "href": "https://doi.org/10.3390/cells9112471"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33202879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33202879"}]}]}]}