{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPRED1 is a critical inhibitor of the RAS–MAPK signaling cascade that exerts its function by directly interacting with key pathway components. In particular, SPRED1 recruits the Ras–GTPase activating protein neurofibromin to the plasma membrane via its EVH1 domain, thereby promoting Ras inactivation. Germline loss‐of‐function mutations in SPRED1 result in Legius syndrome—a condition that phenotypically overlaps with neurofibromatosis type 1 and is characterized by multiple café‐au‐lait macules, axillary freckling, macrocephaly, and learning disabilities. Moreover, detailed structural and mutational analyses of SPRED1 and its related protein family reveal that distinct domains govern its inhibition of RAS signaling and explain the variable clinical phenotypes observed in patients."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various cancers, down‐regulation or inactivation of SPRED1 contributes to aberrant RAS–MAPK pathway activation and disease progression. Reduced SPRED1 expression has been observed in hepatocellular carcinoma, melanoma, acute leukemias, and breast cancers—often correlating with increased tumor invasion, metastasis, and resistance to targeted therapies. In some tumor types, microRNAs (for example, miR‐126, miR‐206, and miR‐21) and epigenetic modifiers target SPRED1, further attenuating its tumor suppressor role. In addition, biochemical studies have identified SPRED1 as a substrate of the tyrosine phosphatase SHP2 and demonstrated that its down‐regulation can promote sustained ERK activity, leading to proliferation and drug resistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in tumor suppression and developmental disorders, SPRED1 is also implicated in the regulation of vascular homeostasis and cytoskeletal dynamics. In endothelial cells, SPRED1 contributes to the orchestration of vascular repair processes and modulates angiogenesis in response to both growth factors and bioactive lipids. Moreover, studies have revealed that SPRED1 regulates cytoskeletal remodeling by interacting with proteins involved in microtubule and F‐actin dynamics, as well as by engaging with receptors that mediate cell–cell signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "36"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "James A J King, Andrew F L Straffon, Giovanna M D'Abaco, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2008.065243"}], "href": "https://doi.org/10.1136/jmg.2008.065243"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19366998"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19366998"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "G Spurlock, E Bennett, N Chuzhanova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2008.065474"}], "href": "https://doi.org/10.1136/jmg.2008.065474"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19443465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19443465"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ludwine Messiaen, Suxia Yao, Hilde Brems, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jama.2009.1663"}], "href": "https://doi.org/10.1001/jama.2009.1663"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19920235"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19920235"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Talia M Muram-Zborovski, David A Stevenson, David H Viskochil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPRED 1 mutations in a neurofibromatosis clinic."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Child Neurol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0883073809359540"}], "href": "https://doi.org/10.1177/0883073809359540"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20179001"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20179001"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Irma B Stowe, Ellen L Mercado, Timothy R Stowe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.190876.112"}], "href": "https://doi.org/10.1101/gad.190876.112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22751498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22751498"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hilde Brems, Eric Pasmant, Rick Van Minkelen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Review and update of SPRED1 mutations causing Legius syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22152"}], "href": "https://doi.org/10.1002/humu.22152"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22753041"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22753041"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Hilde Brems, Eric Legius "}, {"type": "b", "children": [{"type": "t", "text": "Legius syndrome, an Update. 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"}, {"type": "b", "children": [{"type": "t", "text": "Family with Legius syndrome (neurofibromatosis type 1-like syndrome)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dermatol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/1346-8138.12862"}], "href": "https://doi.org/10.1111/1346-8138.12862"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25981987"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25981987"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yasuko Hirata, Hilde Brems, Mayu Suzuki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.703710"}], "href": "https://doi.org/10.1074/jbc.M115.703710"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26635368"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26635368"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Theresia Dunzendorfer-Matt, Ellen L Mercado, Karl Maly, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The first Slovak Legius syndrome patient carrying the SPRED1 gene mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gen Physiol Biophys (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/gpb_2016032"}], "href": "https://doi.org/10.4149/gpb_2016032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28150585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28150585"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Sebastian Führer, Martin Tollinger, Theresia Dunzendorfer-Matt "}, {"type": "b", "children": [{"type": "t", "text": "Pathogenic Mutations Associated with Legius Syndrome Modify the Spred1 Surface and Are Involved in Direct Binding to the Ras Inactivator Neurofibromin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2019.07.038"}], "href": "https://doi.org/10.1016/j.jmb.2019.07.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31401120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31401120"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Donatella Bianchessi, Maria Cristina Ibba, Veronica Saletti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Simultaneous Detection of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "NF1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": ", "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SPRED1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": ", "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "LZTR1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": ", and "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "NF2"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Gene Mutations by Targeted NGS in an Italian Cohort of Suspected NF1 Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes (Basel) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/genes11060671"}], "href": "https://doi.org/10.3390/genes11060671"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32575496"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32575496"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Lisa Pabst, Jennifer Carroll, Warren Lo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Moyamoya syndrome in a child with Legius syndrome: Introducing a cerebral vasculopathy to the SPRED1 phenotype?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.61921"}], "href": "https://doi.org/10.1002/ajmg.a.61921"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33078527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33078527"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "T Yoshida, T Hisamoto, J Akiba, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209635"}], "href": "https://doi.org/10.1038/sj.onc.1209635"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16652141"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16652141"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Carlota A García-Domínguez, Natalia Martínez, Teresa Gragera, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0016787"}], "href": "https://doi.org/10.1371/journal.pone.0016787"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21364986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21364986"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Martina Quintanar-Audelo, Permeen Yusoff, Saravanan Sinniah, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein (SPRED1), a tyrosine-protein phosphatase non-receptor type 11 (SHP2) substrate in the Ras/extracellular signal-regulated kinase (ERK) pathway."}]}, {"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.M110.212662"}], "href": "https://doi.org/10.1074/jbc.M110.212662"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21531714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21531714"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Yvonne E Chiu, Stefanie Dugan, Donald Basel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of Piebaldism, multiple café-au-lait macules, and intertriginous freckling: clinical evidence of a common pathway between KIT and sprouty-related, ena/vasodilator-stimulated phosphoprotein homology-1 domain containing protein 1 (SPRED1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Dermatol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1525-1470.2012.01858.x"}], "href": "https://doi.org/10.1111/j.1525-1470.2012.01858.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23016555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23016555"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Xin Ye, Maged Gomaa Hemida, Ye Qiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-126 promotes coxsackievirus replication by mediating cross-talk of ERK1/2 and Wnt/β-catenin signal pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-013-1411-4"}], "href": "https://doi.org/10.1007/s00018-013-1411-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23811937"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23811937"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "L Olsson, A Castor, M Behrendtz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletions of IKZF1 and SPRED1 are associated with poor prognosis in a population-based series of pediatric B-cell precursor acute lymphoblastic leukemia diagnosed between 1992 and 2011."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/leu.2013.206"}], "href": "https://doi.org/10.1038/leu.2013.206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23823658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23823658"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "E Pasmant, B Gilbert-Dussardier, A Petit, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2013.587"}], "href": "https://doi.org/10.1038/onc.2013.587"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24469042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24469042"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Sriganesh B Sharma, Chen-Chung Lin, Mark K Farrugia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNAs 206 and 21 cooperate to promote RAS-extracellular signal-regulated kinase signaling by suppressing the translation of RASA1 and SPRED1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00480-14"}], "href": "https://doi.org/10.1128/MCB.00480-14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25202123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25202123"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Stephen J Assinder, Daniella Beniamen, Frank J Lovicu "}, {"type": "b", "children": [{"type": "t", "text": "Cosuppression of Sprouty and Sprouty-related negative regulators of FGF signalling in prostate cancer: a working hypothesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2015/827462"}], "href": "https://doi.org/10.1155/2015/827462"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26075267"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26075267"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Priyanka Sharma, Anoop Saraya, Rinu Sharma "}, {"type": "b", "children": [{"type": "t", "text": "Potential diagnostic implications of miR-144 overexpression in human oesophageal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Indian J Med Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4103/0971-5916.191796"}], "href": "https://doi.org/10.4103/0971-5916.191796"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27748283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27748283"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Cheng-Fei Jiang, Zhu-Mei Shi, Dong-Mei Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Estrogen-induced miR-196a elevation promotes tumor growth and metastasis via targeting SPRED1 in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12943-018-0830-0"}], "href": "https://doi.org/10.1186/s12943-018-0830-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29685157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29685157"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Julien Ablain, Mengshu Xu, Harriet Rothschild, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human tumor genomics and zebrafish modeling identify "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SPRED1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " loss as a driver of mucosal melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aau6509"}], "href": "https://doi.org/10.1126/science.aau6509"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30385465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30385465"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Jingwen Sun, Jinjing Zhang, Yue Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Pilot Study of Aberrant CpG Island Hypermethylation of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SPRED1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " in Acute Myeloloid Leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Med Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijms.27757"}], "href": "https://doi.org/10.7150/ijms.27757"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30745814"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30745814"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Julien Ablain, Sixue Liu, Gatien Moriceau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPRED1 deletion confers resistance to MAPK inhibition in melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20201097"}], "href": "https://doi.org/10.1084/jem.20201097"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33306107"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33306107"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Yang Liu, Xiaoxi Fan, Changrui Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPOCK2 and SPRED1 function downstream of EZH2 to impede the malignant progression of lung adenocarcinoma in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-023-00855-0"}], "href": "https://doi.org/10.1007/s13577-023-00855-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36629984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36629984"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Pengfei Zhao, Yating Wang, Xiao Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the miR-627-3p/SPRED1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Med (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11684-023-1004-z"}], "href": "https://doi.org/10.1007/s11684-023-1004-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37434064"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37434064"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Cindy Johne, Dorthe Matenia, Xiao-Yu Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spred1 and TESK1--two new interaction partners of the kinase MARKK/TAO1 that link the microtubule and actin cytoskeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e07-07-0730"}], "href": "https://doi.org/10.1091/mbc.e07-07-0730"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18216281"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18216281"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Lei Zhuang, Peter Villiger, Beat Trueb "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of the receptor FGFRL1 with the negative regulator Spred1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2011.05.006"}], "href": "https://doi.org/10.1016/j.cellsig.2011.05.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21616146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21616146"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Felix Jansen, Xiaoyan Yang, Marion Hoelscher, et al. 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