{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSUFU is a central negative regulator of the Hedgehog signaling pathway that functions by directly binding to Gli transcription factors, thereby sequestering them and controlling their subcellular localization and transcriptional output. Structural and biochemical studies have revealed that SUFU undergoes dramatic conformational rearrangements upon Gli binding and can nucleate multiprotein repressor complexes—mechanisms essential for proper embryonic patterning and the maintenance of cellular homeostasis. These foundational observations underscore SUFU’s critical role as a tumor‐suppressor by tightly modulating Hedgehog pathway activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSUFU’s regulatory activity is modulated at multiple levels. Post‐translational modifications such as phosphorylation—mediated by kinases including PKA and GSK3β—and ubiquitination, via E3 ligases like Itch and Fbxl17, dynamically influence its stability and capacity to interact with Gli proteins. In addition, emerging evidence demonstrates that aberrant expression of several microRNAs (for example, miR‑378, miR‑423‑5p, miR‑194, miR‑214, miR‑324‑5p, miR‑224, and miR‑342‑3p) in diverse tumor types directly targets SUFU, thereby releasing Gli factors from inhibition and enabling oncogenic pathway activation. Additional modulators—including binding partners such as Rab23, RIOK3, and anti‐apoptotic BCL‑2 family proteins—further fine‑tune SUFU’s function, emphasizing the complexity of its regulation in both normal and diseased cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, both germline and somatic alterations in SUFU—or its deregulation by upstream oncogenic signals—have been implicated in a variety of human neoplasms. Inherited mutations in SUFU predispose to pediatric medulloblastoma and are frequently observed in patients with Gorlin syndrome and related nevoid basal cell carcinoma phenotypes, while loss‐of‑function events and misregulation of SUFU contribute to tumor progression in meningioma, basal cell carcinoma, glioblastoma, and even endocrine and gastrointestinal cancers by unleashing hyperactive Hedgehog (and occasionally Wnt) signaling. Such observations, together with reports of disrupted SUFU expression in diverse tissues (including esophageal epithelium, the retina, and craniofacial structures), underscore its pivotal role in controlling proliferation and differentiation. Moreover, altered SUFU function—as seen in cases with additional mutations or loss of heterozygosity—and its interaction with proteins involved in cell‐cycle control contribute to complex genotype–phenotype correlations that impact cancer susceptibility and aggressiveness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "40"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Steven Yan Cheng, J Michael Bishop "}, {"type": "b", "children": [{"type": "t", "text": "Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.082096999"}], "href": "https://doi.org/10.1073/pnas.082096999"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11960000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11960000"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michael D Taylor, Ling Liu, Corey Raffel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in SUFU predispose to medulloblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng916"}], "href": "https://doi.org/10.1038/ng916"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12068298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12068298"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kenji Kasai, Shingo Inaguma, Akiko Yoneyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SCL/TAL1 interrupting locus derepresses GLI1 from the negative control of suppressor-of-fused in pancreatic cancer cell."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-6661"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-6661"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18829525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18829525"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yan Zhang, Lin Fu, Xiaolong Qi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insight into the mutual recognition and regulation between Suppressor of Fused and Gli/Ci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms3608"}], "href": "https://doi.org/10.1038/ncomms3608"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24217340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24217340"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Amy L Cherry, Csaba Finta, Mikael Karlström, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Crystallogr D Biol Crystallogr (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1107/S0907444913028473"}], "href": "https://doi.org/10.1107/S0907444913028473"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24311597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24311597"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Daniel Y Lee, Zhaoqun Deng, Chia-Hui Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0706901104"}], "href": "https://doi.org/10.1073/pnas.0706901104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18077375"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18077375"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "S Yue, Y Chen, S Y Cheng "}, {"type": "b", "children": [{"type": "t", "text": "Hedgehog signaling promotes the degradation of tumor suppressor Sufu through the ubiquitin-proteasome pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2008.403"}], "href": "https://doi.org/10.1038/onc.2008.403"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18997815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18997815"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yan Chen, Shen Yue, Lu Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dual Phosphorylation of suppressor of fused (Sufu) by PKA and GSK3beta regulates its stability and localization in the primary cilium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.217604"}], "href": "https://doi.org/10.1074/jbc.M110.217604"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21317289"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21317289"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sumin Chi, Guorui Xie, Hailan Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2012.02.004"}], "href": "https://doi.org/10.1016/j.cellsig.2012.02.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22365972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22365972"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Melanie Tariki, Sarah Alexandra Wieczorek, Philipp Schneider, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RIO kinase 3 acts as a SUFU-dependent positive regulator of Hedgehog signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2013.08.037"}], "href": "https://doi.org/10.1016/j.cellsig.2013.08.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24018050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24018050"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Madalina Raducu, Ella Fung, Sébastien Serres, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and medulloblastoma development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201593374"}], "href": "https://doi.org/10.15252/embj.201593374"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27234298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27234298"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yao Wang, Yong Li, Guanghui Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nek2A phosphorylates and stabilizes SuFu: A new strategy of Gli2/Hedgehog signaling regulatory mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2016.06.010"}], "href": "https://doi.org/10.1016/j.cellsig.2016.06.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27297360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27297360"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Fatouma Alimirah, Xinjian Peng, Akash Gupta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crosstalk between the vitamin D receptor (VDR) and miR-214 in regulating SuFu, a hedgehog pathway inhibitor in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2016.08.012"}], "href": "https://doi.org/10.1016/j.yexcr.2016.08.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27693451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27693451"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Yin Peng, Xiaojing Zhang, Qiang Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiRNA-194 activates the Wnt/β-catenin signaling pathway in gastric cancer by targeting the negative Wnt regulator, SUFU."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2016.10.035"}], "href": "https://doi.org/10.1016/j.canlet.2016.10.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27810403"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27810403"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Nicole M Urman, Amar Mirza, Scott X Atwood, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor-Derived Suppressor of Fused Mutations Reveal Hedgehog Pathway Interactions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0168031"}], "href": "https://doi.org/10.1371/journal.pone.0168031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28030567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28030567"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Mengqi Huang, Ying Qing, Qi Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-342-3p elevates osteogenic differentiation of umbilical cord mesenchymal stem cells via inhibiting Sufu in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.07.163"}], "href": "https://doi.org/10.1016/j.bbrc.2017.07.163"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28765042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28765042"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Xiaobo Miao, Hai Gao, Shiyong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of microRNA-224 -inhibites growth and epithelial-to-mesenchymal transition phenotype -via modulating SUFU expression in bladder cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Macromol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ijbiomac.2017.07.184"}], "href": "https://doi.org/10.1016/j.ijbiomac.2017.07.184"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28780419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28780419"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Xiaofeng Wu, Li-Shu Zhang, Jason Toombs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3616"}], "href": "https://doi.org/10.1038/ncb3616"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28945232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28945232"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Paola Infante, Roberta Faedda, Flavia Bernardi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Itch/β-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-03339-0"}], "href": "https://doi.org/10.1038/s41467-018-03339-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29515120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29515120"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Huan Yang, Hailong Fu, Bo Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosomal miR-423-5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.22838"}], "href": "https://doi.org/10.1002/mc.22838"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29749061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29749061"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Liping Ma, Xiaoxue Yang, Rong Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-214 promotes hepatic stellate cell activation and liver fibrosis by suppressing Sufu expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-0752-1"}], "href": "https://doi.org/10.1038/s41419-018-0752-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29915227"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29915227"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Yin Peng, Xiaojing Zhang, Huijuan Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SUFU mediates EMT and Wnt/β-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2020.1826632"}], "href": "https://doi.org/10.1080/15384101.2020.1826632"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33017570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33017570"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Michael D Taylor, Xiaoyun Zhang, Ling Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Failure of a medulloblastoma-derived mutant of SUFU to suppress WNT signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1207605"}], "href": "https://doi.org/10.1038/sj.onc.1207605"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15077159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15077159"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Kyung Hee Kim, Jin Man Kim, Yoon-La Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of sonic hedgehog signaling molecules in normal, hyperplastic and carcinomatous endometrium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Int (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1440-1827.2009.02366.x"}], "href": "https://doi.org/10.1111/j.1440-1827.2009.02366.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19432668"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19432668"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "L Pastorino, P Ghiorzo, S Nasti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a SUFU germline mutation in a family with Gorlin syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.32944"}], "href": "https://doi.org/10.1002/ajmg.a.32944"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19533801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19533801"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Laurence Brugières, Gaëlle Pierron, Agnès Chompret, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2009.067751"}], "href": "https://doi.org/10.1136/jmg.2009.067751"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19833601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19833601"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Ingrid Slade, Anne Murray, Sandra Hanks, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heterogeneity of familial medulloblastoma and contribution of germline PTCH1 and SUFU mutations to sporadic medulloblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fam Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10689-010-9411-0"}], "href": "https://doi.org/10.1007/s10689-010-9411-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21188540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21188540"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Laurence Brugières, Audrey Remenieras, Gaëlle Pierron, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2011.38.7258"}], "href": "https://doi.org/10.1200/JCO.2011.38.7258"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22508808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22508808"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Mervi Aavikko, Song-Ping Li, Silva Saarinen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of SUFU function in familial multiple meningioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.07.015"}], "href": "https://doi.org/10.1016/j.ajhg.2012.07.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22958902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22958902"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Miriam J Smith, Christian Beetz, Simon G Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2014.58.2569"}], "href": "https://doi.org/10.1200/JCO.2014.58.2569"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25403219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25403219"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "D Gareth Evans, Deemesh Oudit, Miriam J Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "First evidence of genotype-phenotype correlations in Gorlin syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2017-104669"}], "href": "https://doi.org/10.1136/jmedgenet-2017-104669"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28596197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28596197"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "A J Huq, M Walsh, B Rajagopalan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in SUFU and PTCH1 genes may cause different cutaneous cancer predisposition syndromes: similar, but not the same."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fam Cancer (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10689-018-0073-7"}], "href": "https://doi.org/10.1007/s10689-018-0073-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29356994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29356994"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Yin Peng, Xiaojing Zhang, Huijuan Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of miR‑194 suppresses the Wnt/β‑catenin signalling pathway in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2018.6773"}], "href": "https://doi.org/10.3892/or.2018.6773"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30542715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30542715"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Huiqing Zeng, Jinping Jia, Aimin Liu "}, {"type": "b", "children": [{"type": "t", "text": "Coordinated translocation of mammalian Gli proteins and suppressor of fused to the primary cilium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0015900"}], "href": "https://doi.org/10.1371/journal.pone.0015900"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21209912"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21209912"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Yasuyuki Shimada, Ken-ichi Katsube, Yuji Kabasawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated genotypic analysis of hedgehog-related genes identifies subgroups of keratocystic odontogenic tumor with distinct clinicopathological features."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0070995"}], "href": "https://doi.org/10.1371/journal.pone.0070995"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23951062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23951062"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Chihiro Kijima, Toshiyuki Miyashita, Maiko Suzuki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two cases of nevoid basal cell carcinoma syndrome associated with meningioma caused by a PTCH1 or SUFU germline mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fam Cancer (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10689-012-9548-0"}], "href": "https://doi.org/10.1007/s10689-012-9548-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22829011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22829011"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Ling Yang, Yuehong Bian, Shuhong Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of signature genes for detecting hedgehog pathway activation in esophageal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Oncol Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12253-010-9337-8"}], "href": "https://doi.org/10.1007/s12253-010-9337-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21210262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21210262"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "C Klingelhöffer, A Reck, T Ettl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The parathyroid hormone-related protein is secreted during the osteogenic differentiation of human dental follicle cells and inhibits the alkaline phosphatase activity and the expression of DLX3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tissue Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tice.2016.05.007"}], "href": "https://doi.org/10.1016/j.tice.2016.05.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27368119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27368119"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Joshua M Schulman, Dennis H Oh, J Zachary Sanborn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple Hereditary Infundibulocystic Basal Cell Carcinoma Syndrome Associated With a Germline SUFU Mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA Dermatol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jamadermatol.2015.4233"}], "href": "https://doi.org/10.1001/jamadermatol.2015.4233"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26677003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26677003"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Gary T ZeRuth, Xiao-Ping Yang, Anton M Jetten "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of the transactivation function and stability of Krüppel-like zinc finger protein Gli-similar 3 (Glis3) by Suppressor of Fused."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.224964"}], "href": "https://doi.org/10.1074/jbc.M111.224964"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21543335"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21543335"}]}]}]}