{"id":"https://openalex.org/W4389026659","doi":"https://doi.org/10.1096/fasebj.30.1_supplement.226.3","title":"Twist1 triggers PKD1 expression to promote metastatic dissemination in breast cancer","display_name":"Twist1 triggers PKD1 expression to promote metastatic dissemination in breast cancer","publication_year":2016,"publication_date":"2016-04-01","ids":{"openalex":"https://openalex.org/W4389026659","doi":"https://doi.org/10.1096/fasebj.30.1_supplement.226.3"},"language":"en","primary_location":{"id":"doi:10.1096/fasebj.30.1_supplement.226.3","doi":"https://doi.org/10.1096/fasebj.30.1_supplement.226.3","is_oa":false,"landing_page_url":"https://doi.org/10.1096/fasebj.30.1_supplement.226.3","pdf_url":null,"source":{"id":"https://openalex.org/S25293849","display_name":"The FASEB Journal","issn_l":"0892-6638","issn":["0892-6638","1530-6860"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-c","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The FASEB Journal","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5087398585","display_name":"Dan Georgess","orcid":"https://orcid.org/0000-0003-3075-4527","observed_orcids":["https://orcid.org/0000-0003-3075-4527"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I2799853436","display_name":"Johns Hopkins Medicine","ror":"https://ror.org/037zgn354","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dan Georgess","raw_affiliation_strings":["Departments of Cell Biology Oncology and Biomedical Engineering; Center for Cell Dynamics Johns Hopkins University School of Medicine Baltimore MD","Departments of Cell Biology, Oncology and Biomedical Engineering"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Cell Biology Oncology and Biomedical Engineering; Center for Cell Dynamics Johns Hopkins University School of Medicine Baltimore MD","institution_ids":["https://openalex.org/I145311948","https://openalex.org/I2799853436"]},{"raw_affiliation_string":"Departments of Cell Biology, Oncology and Biomedical Engineering","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5089385495","display_name":"Orit Katarina Sirka","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I2799853436","display_name":"Johns Hopkins Medicine","ror":"https://ror.org/037zgn354","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"O. Katarina Sirka","raw_affiliation_strings":["Departments of Cell Biology Oncology and Biomedical Engineering; Center for Cell Dynamics Johns Hopkins University School of Medicine Baltimore MD","Departments of Cell Biology, Oncology and Biomedical Engineering"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Cell Biology Oncology and Biomedical Engineering; Center for Cell Dynamics Johns Hopkins University School of Medicine Baltimore MD","institution_ids":["https://openalex.org/I145311948","https://openalex.org/I2799853436"]},{"raw_affiliation_string":"Departments of Cell Biology, Oncology and Biomedical Engineering","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5015473684","display_name":"Neil M. Neumann","orcid":"https://orcid.org/0000-0001-9779-7754","observed_orcids":["https://orcid.org/0000-0001-9779-7754"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I2799853436","display_name":"Johns Hopkins Medicine","ror":"https://ror.org/037zgn354","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Neil M. Neumann","raw_affiliation_strings":["Departments of Cell Biology Oncology and Biomedical Engineering; Center for Cell Dynamics Johns Hopkins University School of Medicine Baltimore MD","Departments of Cell Biology, Oncology and Biomedical Engineering"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Cell Biology Oncology and Biomedical Engineering; Center for Cell Dynamics Johns Hopkins University School of Medicine Baltimore MD","institution_ids":["https://openalex.org/I145311948","https://openalex.org/I2799853436"]},{"raw_affiliation_string":"Departments of Cell Biology, Oncology and Biomedical Engineering","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063990076","display_name":"Eliah R. Shamir","orcid":"https://orcid.org/0000-0002-2417-3294","observed_orcids":["https://orcid.org/0000-0002-2417-3294"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I2799853436","display_name":"Johns Hopkins Medicine","ror":"https://ror.org/037zgn354","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Eliah R. Shamir","raw_affiliation_strings":["Departments of Cell Biology Oncology and Biomedical Engineering; Center for Cell Dynamics Johns Hopkins University School of Medicine Baltimore MD","Departments of Cell Biology, Oncology and Biomedical Engineering"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Cell Biology Oncology and Biomedical Engineering; Center for Cell Dynamics Johns Hopkins University School of Medicine Baltimore MD","institution_ids":["https://openalex.org/I145311948","https://openalex.org/I2799853436"]},{"raw_affiliation_string":"Departments of Cell Biology, Oncology and Biomedical Engineering","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5084041667","display_name":"Andrew J. Ewald","orcid":"https://orcid.org/0000-0002-1964-0740","observed_orcids":["https://orcid.org/0000-0002-1964-0740"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I2799853436","display_name":"Johns Hopkins Medicine","ror":"https://ror.org/037zgn354","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Andrew J. Ewald","raw_affiliation_strings":["Departments of Cell Biology Oncology and Biomedical Engineering; Center for Cell Dynamics Johns Hopkins University School of Medicine Baltimore MD","Departments of Cell Biology, Oncology and Biomedical Engineering"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Cell Biology Oncology and Biomedical Engineering; Center for Cell Dynamics Johns Hopkins University School of Medicine Baltimore MD","institution_ids":["https://openalex.org/I145311948","https://openalex.org/I2799853436"]},{"raw_affiliation_string":"Departments of Cell Biology, Oncology and Biomedical Engineering","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":3740,"currency":"USD","value_usd":3740},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.42664889,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"30","issue":"S1","first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10336","display_name":"Cancer Cells and Metastasis","score":0.9839000105857849,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10336","display_name":"Cancer Cells and Metastasis","score":0.9839000105857849,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T13437","display_name":"Mechanisms of cancer metastasis","score":0.012799999676644802,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11501","display_name":"TGF-\u03b2 signaling in diseases","score":0.0010000000474974513,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/twist1","display_name":"TWIST1","score":0.9750000238418579},{"id":"https://openalex.org/keywords/pkd1","display_name":"PKD1","score":0.9390000104904175},{"id":"https://openalex.org/keywords/protein-kinase-d","display_name":"protein kinase D","score":0.8270000219345093},{"id":"https://openalex.org/keywords/breast-cancer-metastasis","display_name":"breast cancer metastasis","score":0.9449999928474426},{"id":"https://openalex.org/keywords/mammary-organoids","display_name":"mammary organoids","score":0.7860000133514404},{"id":"https://openalex.org/keywords/go6976","display_name":"G\u00f66976","score":0.9010000228881836},{"id":"https://openalex.org/keywords/protein-kinase-c","display_name":"protein kinase C","score":0.722000002861023},{"id":"https://openalex.org/keywords/gene-expression-profiling","display_name":"gene expression profiling","score":0.41999998688697815},{"id":"https://openalex.org/keywords/tumor-invasion","display_name":"tumor invasion","score":0.5419999957084656},{"id":"https://openalex.org/keywords/organotypic-culture","display_name":"organotypic culture","score":0.5139999985694885},{"id":"https://openalex.org/keywords/pkd2","display_name":"PKD2","score":0.4180000126361847},{"id":"https://openalex.org/keywords/sorafenib","display_name":"sorafenib","score":0.6000000238418579}],"concepts":[{"id":"https://openalex.org/C173396325","wikidata":"https://www.wikidata.org/wiki/Q1501275","display_name":"Gene knockdown","level":3,"score":0.6778374910354614},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6305202841758728},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6199620962142944},{"id":"https://openalex.org/C31695470","wikidata":"https://www.wikidata.org/wiki/Q11293125","display_name":"Organoid","level":2,"score":0.6078445911407471},{"id":"https://openalex.org/C2779013556","wikidata":"https://www.wikidata.org/wiki/Q181876","display_name":"Metastasis","level":3,"score":0.5761740803718567},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.5007474422454834},{"id":"https://openalex.org/C2778893926","wikidata":"https://www.wikidata.org/wiki/Q575849","display_name":"Twist transcription factor","level":5,"score":0.4948675036430359},{"id":"https://openalex.org/C200786668","wikidata":"https://www.wikidata.org/wiki/Q3498029","display_name":"Invadopodia","level":4,"score":0.46250101923942566},{"id":"https://openalex.org/C529295009","wikidata":"https://www.wikidata.org/wiki/Q41301","display_name":"Epithelium","level":2,"score":0.43457120656967163},{"id":"https://openalex.org/C76419328","wikidata":"https://www.wikidata.org/wiki/Q74419","display_name":"Epithelial\u2013mesenchymal transition","level":4,"score":0.3641250431537628},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.33296799659729004},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3255869150161743},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.30009979009628296},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.1846102476119995},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.11046144366264343}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1096/fasebj.30.1_supplement.226.3","doi":"https://doi.org/10.1096/fasebj.30.1_supplement.226.3","is_oa":false,"landing_page_url":"https://doi.org/10.1096/fasebj.30.1_supplement.226.3","pdf_url":null,"source":{"id":"https://openalex.org/S25293849","display_name":"The FASEB Journal","issn_l":"0892-6638","issn":["0892-6638","1530-6860"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-c","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The FASEB Journal","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.8560000061988831,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320307514","display_name":"American Association of Anatomists","ror":"https://ror.org/04v1psm68"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2983651791","https://openalex.org/W2762693247","https://openalex.org/W1482495029","https://openalex.org/W4210608643","https://openalex.org/W2535003418","https://openalex.org/W2152965684","https://openalex.org/W2571749287","https://openalex.org/W2036008499","https://openalex.org/W2129232821","https://openalex.org/W2755874090"],"abstract_inverted_index":{"Metastasis":[0],"is":[1,21,37,197,205,399,408],"defined":[2],"by":[3,42,116,410],"a":[4,144,159,312,354,366],"subset":[5],"of":[6,72,87,105,123,140,143,222,239,242,270,288,323,349,403,417],"cells":[7,351],"disseminating":[8],"from":[9,81,227,306,341,353,413],"the":[10,64,225,252,359,414,420],"epithelium,":[11,66],"and":[12,27,107,180,241,308,330,334,391,406,419],"eventually":[13],"colonizing":[14],"distant":[15],"organs.":[16],"The":[17],"transcription":[18],"factor":[19],"Twist1":[20,36,62,88,117,371],"overexpressed":[22],"in":[23,54,63,90,158,162,176,184,200,208,218,295,318,337,376],"metastatic":[24,385],"breast":[25,178,185,297],"cancers":[26],"its":[28,46,228,243],"expression":[29,89,375],"correlates":[30],"with":[31,153,251,315],"poor":[32],"patient":[33],"prognosis.":[34],"Although":[35],"known":[38],"for":[39,136],"promoting":[40],"metastasis":[41],"controlling":[43],"gene":[44,48],"expression,":[45],"exact":[47],"targets":[49],"that":[50,78,113,195,269,311],"are":[51,57,114],"functionally":[52],"involved":[53],"cell":[55,99,389],"dissemination":[56,100,257,338,390],"still":[58],"controversial.":[59],"To":[60,291],"study":[61],"mammary":[65,73,202,356,378],"we":[67,79,299,309],"used":[68],"3D":[69],"organotypic":[70],"culture":[71],"epithelium":[74,179],"fragments,":[75],"called":[76],"\u201corganoids\u201d,":[77],"isolate":[80],"an":[82,319,400],"inducible":[83],"TetO\u2010Twist1":[84],"mouse.":[85],"Induction":[86],"these":[91,124,293],"organoids":[92,109,203],"was":[93,166,170,215,264],"sufficient":[94],"to":[95,173,181,358],"drive":[96,383],"robust":[97],"epithelial":[98],"through":[101],"extracellular":[102],"matrix.":[103],"RNAseq":[104],"Twist1\u2010induced":[106,209],"control":[108],"revealed":[110],"107":[111,125],"genes":[112],"upregulated":[115,206],"at":[118],"genome\u2010wide":[119],"significance.":[120],"For":[121],"9":[122],"genes,":[126],"specific":[127],"small":[128],"molecule":[129],"inhibitors":[130],"were":[131],"commercially":[132],"available":[133],"thus":[134],"allowing":[135,187],"immediate":[137],"dose\u2010response":[138],"assay":[139],"dissemination.":[141,163,235],"Inhibition":[142],"single":[145,313,350],"target":[146],"\u2013":[147,152],"protein":[148,247],"kinase":[149,248],"D1":[150],"(PKD1)":[151],"compound":[154,253],"nb\u2010KB":[155],"142\u201070":[156],"resulted":[157,317],"significant":[160],"decrease":[161,322,336],"This":[164],"result":[165],"surprising":[167],"because":[168],"PKD1":[169,196,223,240,374,381],"previously":[171],"thought":[172],"be":[174,182],"expressed":[175],"normal":[177,201,285],"downregulated":[183],"cancer":[186],"tumor":[188,357],"metastasis.":[189],"However,":[190],"our":[191,363],"immunoblotting":[192],"data":[193,364],"showed":[194],"barely":[198],"detectable":[199],"but":[204],"7\u2010fold":[207],"organoids,":[210],"while":[211],"family":[212],"member":[213],"PKD2":[214],"not":[216,283],"detected":[217],"either.":[219],"shRNA":[220],"knockdown":[221],"confirmed":[224],"outcome":[226],"drug":[229],"inhibition":[230],"as":[231,275,388],"it":[232],"dramatically":[233],"inhibited":[234],"Importantly,":[236],"simultaneous":[237],"targeting":[238],"direct":[244],"upstream":[245],"activator":[246],"C":[249],"(PKC)":[250],"G\u00f6\u20106976":[254,281,316,343],"completely":[255],"blocked":[256],"(IC50":[258],"11.5":[259],"nM).":[260],"G\u00f6\u20106976's":[261],"anti\u2010disseminative":[262],"effect":[263],"significantly":[265],"more":[266],"potent":[267],"than":[268],"other":[271],"kinase\u2010targeting":[272],"drugs":[273],"such":[274,387],"FDA\u2010approved":[276],"Sorafenib;":[277],"and,":[278],"unlike":[279],"Sorafenib,":[280],"did":[282],"abolish":[284],"branching":[286],"morphogenesis":[287],"wildtype":[289],"epithelium.":[290],"validate":[292],"findings":[294],"human":[296],"cancer,":[298],"organotypically":[300],"cultured":[301],"primary":[302,377],"tumors":[303,329],"surgically":[304],"removed":[305],"patients,":[307],"found":[310],"treatment":[314],"overall":[320],"62%":[321],"invasion":[324],"(N=":[325],"6;":[326],"4":[327],"ER+/PR+":[328],"2":[331],"ER\u2010/PR\u2010/Her2\u2010":[332],"tumors)":[333],"86%":[335],"(N=2).":[339],"Independently":[340],"dissemination,":[342],"also":[344],"reduced":[345],"colony":[346],"formation":[347],"potential":[348],"isolated":[352],"secondary/metastatic":[355],"lymph":[360],"node.":[361],"Altogether,":[362],"suggest":[365],"new":[367],"working":[368],"model":[369],"where":[370],"can":[372,382],"trigger":[373],"tumors,":[379],"then":[380],"distinct":[384],"processes":[386],"proliferation.":[392],"Support":[393],"or":[394],"Funding":[395],"Information":[396],"Dan":[397],"Georgess":[398],"American":[401,415],"Association":[402,416],"Anatomists":[404,418],"Scholar":[405],"he":[407],"funded":[409],"postdoctoral":[411],"fellowships":[412],"Suzan":[421],"G.":[422],"Komen":[423],"Foundation.":[424]},"counts_by_year":[],"updated_date":"2026-08-21T09:56:20.448147","created_date":"2023-11-27T00:00:00"}
