{"id":"https://openalex.org/W7004760084","doi":null,"title":"Oncogenic Kras And Telomere Biology In Crc Progression","display_name":"Oncogenic Kras And Telomere Biology In Crc Progression","publication_year":2023,"publication_date":"2023-12-01","ids":{"openalex":"https://openalex.org/W7004760084"},"language":"en","primary_location":{"id":"pmh:oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2367","doi":null,"is_oa":false,"landing_page_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1310","pdf_url":null,"source":{"id":"https://openalex.org/S4377196655","display_name":"Digital Commons-TMC (Texas Medical Center)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1337852284","host_organization_name":"Texas Medical Center","host_organization_lineage":["https://openalex.org/I1337852284"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Dissertations & Theses (Open Access)","raw_type":"text"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"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/A5008120994","display_name":"Ronald Anthony DePinho","orcid":"https://orcid.org/0000-0002-5625-577X","observed_orcids":["https://orcid.org/0000-0002-5625-577X"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"DePinho, Ronald","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5008120994"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":true,"primary_topic":{"id":"https://openalex.org/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":0.3747999966144562,"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/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":0.3747999966144562,"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/T10937","display_name":"Telomeres, Telomerase, and Senescence","score":0.14720000326633453,"subfield":{"id":"https://openalex.org/subfields/1307","display_name":"Cell 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/T10336","display_name":"Cancer Cells and Metastasis","score":0.120899997651577,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/kras-oncogene","display_name":"K-ras oncogene","score":0.7590000033378601},{"id":"https://openalex.org/keywords/colorectal-cancer","display_name":"colorectal cancer","score":0.8029999732971191},{"id":"https://openalex.org/keywords/metastatic-colorectal-cancer","display_name":"metastatic colorectal cancer","score":0.824999988079071},{"id":"https://openalex.org/keywords/telomere-biology","display_name":"telomere biology","score":0.7039999961853027},{"id":"https://openalex.org/keywords/tert","display_name":"telomerase reverse transcriptase","score":0.8949999809265137},{"id":"https://openalex.org/keywords/adipogenic-differentiation","display_name":"adipogenesis","score":0.7490000128746033},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.9049999713897705},{"id":"https://openalex.org/keywords/angiogenesis","display_name":"angiogenesis","score":0.9070000052452087},{"id":"https://openalex.org/keywords/tgf-beta-signaling","display_name":"TGF-beta signaling","score":0.640999972820282},{"id":"https://openalex.org/keywords/myeloid-derived-suppressor-cells","display_name":"myeloid-derived suppressor cells","score":0.9990000128746033},{"id":"https://openalex.org/keywords/antitumor-immunity","display_name":"antitumor immunity","score":0.7179999947547913}],"concepts":[{"id":"https://openalex.org/C2781187634","wikidata":"https://www.wikidata.org/wiki/Q20969980","display_name":"KRAS","level":4,"score":0.6985999941825867},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6879000067710876},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6485999822616577},{"id":"https://openalex.org/C177336024","wikidata":"https://www.wikidata.org/wiki/Q14872779","display_name":"Telomere","level":3,"score":0.6089000105857849},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.5271999835968018},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.5157999992370605},{"id":"https://openalex.org/C2779013556","wikidata":"https://www.wikidata.org/wiki/Q181876","display_name":"Metastasis","level":3,"score":0.498199999332428},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.48080000281333923},{"id":"https://openalex.org/C2780394083","wikidata":"https://www.wikidata.org/wiki/Q539568","display_name":"Angiogenesis","level":2,"score":0.4745999872684479},{"id":"https://openalex.org/C179185449","wikidata":"https://www.wikidata.org/wiki/Q219699","display_name":"Suppressor","level":3,"score":0.4260999858379364},{"id":"https://openalex.org/C2779256057","wikidata":"https://www.wikidata.org/wiki/Q16909647","display_name":"Tumor progression","level":3,"score":0.40450000762939453},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.36899998784065247},{"id":"https://openalex.org/C2781018059","wikidata":"https://www.wikidata.org/wiki/Q207609","display_name":"Oncogene","level":4,"score":0.36730000376701355},{"id":"https://openalex.org/C145103041","wikidata":"https://www.wikidata.org/wiki/Q1151519","display_name":"Embryonic stem cell","level":3,"score":0.358599990606308},{"id":"https://openalex.org/C180754005","wikidata":"https://www.wikidata.org/wiki/Q80726","display_name":"Allele","level":3,"score":0.3547999858856201},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.35019999742507935},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.34470000863075256},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.3382999897003174},{"id":"https://openalex.org/C2778287671","wikidata":"https://www.wikidata.org/wiki/Q7852676","display_name":"Tumor initiation","level":4,"score":0.32820001244544983},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.3149999976158142},{"id":"https://openalex.org/C102230213","wikidata":"https://www.wikidata.org/wiki/Q430117","display_name":"Transgene","level":3,"score":0.3043999969959259},{"id":"https://openalex.org/C94581717","wikidata":"https://www.wikidata.org/wiki/Q331839","display_name":"Telomerase","level":3,"score":0.30070000886917114},{"id":"https://openalex.org/C2780283643","wikidata":"https://www.wikidata.org/wiki/Q2110267","display_name":"Primary tumor","level":4,"score":0.3003000020980835},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.2948000133037567},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.2946000099182129},{"id":"https://openalex.org/C555283112","wikidata":"https://www.wikidata.org/wiki/Q1637543","display_name":"Carcinogenesis","level":3,"score":0.29159998893737793},{"id":"https://openalex.org/C2778220009","wikidata":"https://www.wikidata.org/wiki/Q160105","display_name":"Cervical cancer","level":3,"score":0.28619998693466187},{"id":"https://openalex.org/C62112901","wikidata":"https://www.wikidata.org/wiki/Q189159","display_name":"Cell growth","level":2,"score":0.2727000117301941},{"id":"https://openalex.org/C2778264664","wikidata":"https://www.wikidata.org/wiki/Q422445","display_name":"Tumor suppressor gene","level":4,"score":0.2660999894142151},{"id":"https://openalex.org/C143589142","wikidata":"https://www.wikidata.org/wiki/Q2617554","display_name":"Loss of heterozygosity","level":4,"score":0.26080000400543213},{"id":"https://openalex.org/C147969180","wikidata":"https://www.wikidata.org/wiki/Q5014579","display_name":"CTL*","level":4,"score":0.258899986743927}],"mesh":[],"locations_count":1,"locations":[{"id":"pmh:oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2367","doi":null,"is_oa":false,"landing_page_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1310","pdf_url":null,"source":{"id":"https://openalex.org/S4377196655","display_name":"Digital Commons-TMC (Texas Medical Center)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1337852284","host_organization_name":"Texas Medical Center","host_organization_lineage":["https://openalex.org/I1337852284"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Dissertations & Theses (Open Access)","raw_type":"text"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2597230258","https://openalex.org/W4387115132","https://openalex.org/W2595590650","https://openalex.org/W4393989465","https://openalex.org/W4386263376","https://openalex.org/W4404185326","https://openalex.org/W7113028204","https://openalex.org/W2052820539","https://openalex.org/W2972884351","https://openalex.org/W4393157829"],"abstract_inverted_index":{"While":[0,418],"colorectal":[1],"cancer":[2,102,108,115,158,264],"(CRC)":[3],"patients":[4,27],"diagnosed":[5,28],"with":[6,29,79,160,364,451],"localized":[7],"stage":[8],"disease":[9],"(as":[10],"defined":[11],"by":[12,113,386],"SEER)":[13],"have":[14,137,193,227,256,269,463],"a":[15,64,195,232,287,313,326,441],"5-year":[16],"survival":[17],"rate":[18,22,332],"of":[19,88,164,168,188,202,237,252,277,289,322,333,349,368,396,401,408,421,434,459,480,504],"90%,":[20],"this":[21],"plunges":[23],"to":[24,38,46,60,93,150,244,300,338,377,405,473,476,500],"14%":[25],"for":[26,68,171,443,508],"metastatic":[30,172,301,331,416,453],"CRC.":[31,48,173],"Consequently,":[32,211],"there":[33],"is":[34,304,362],"an":[35,80,200,347,350,413],"immediate":[36],"imperative":[37],"elucidate":[39],"the":[40,44,55,124,161,166,176,208,249,258,273,399,406,419,425,432,435,452,456,469,478,491,498,502],"mechanisms":[41,155,260],"that":[42,306],"drive":[43,266],"transition":[45],"advanced":[47,509],"Human":[49],"CRCs":[50],"carrying":[51],"oncogenic":[52],"mutations":[53],"in":[54,73,100,111,141,207,280,316,415,486],"KRAS":[56,310,323],"oncogene,":[57],"henceforth":[58],"referred":[59,243],"as":[61,94,245,474],"KRAS*,":[62],"exhibit":[63,325],"25%":[65],"higher":[66],"propensity":[67],"developing":[69],"liver":[70],"metastases.":[71,318],"Similarly,":[72],"our":[74,148,212,357],"CRC":[75,190,283,297,510],"mouse":[76,216,295,394],"model,":[77,360],"engineered":[78,363],"inducible":[81,351],"Kras*":[82],"transgene":[83],"and":[84,90,104,119,152,179,185,199,205,219,240,268,294,370,381,412,447,483,489],"conditional":[85,365],"null":[86,366],"alleles":[87,367],"Apc":[89,369],"Tp53":[91],"(referred":[92,472],"iKAP),":[95],"KRAS*":[96,136,296],"has":[97,146],"been":[98],"implicated":[99],"driving":[101,317,487],"progression":[103,299],"metastasis.":[105],"Mechanistically,":[106],"KRAS*-driven":[107,157,282],"metastasis":[109,488],"operates,":[110],"part,":[112],"activating":[114],"cell-intrinsic":[116],"TGF\u03b2":[117],"signaling":[118],"suppressing":[120],"anti-tumoral":[121],"immunity":[122],"through":[123,261],"IRF2-CXCL3":[125],"axis,":[126],"which":[127,262,361],"recruits":[128],"myeloid-derived":[129],"suppressor":[130],"cells.":[131],"Regrettably,":[132],"emerging":[133],"therapies":[134],"targeting":[135],"demonstrated":[138],"limited":[139],"efficacy":[140],"clinical":[142],"settings.":[143],"This":[144,372],"challenge":[145],"spurred":[147],"efforts":[149],"identify":[151],"validate":[153],"additional":[154],"underpinning":[156],"progression,":[159],"ultimate":[162],"aim":[163],"expanding":[165],"array":[167],"therapeutic":[169,506],"targets":[170,507],"By":[174],"utilizing":[175],"iKAP":[177,223],"model":[178,427,471],"employing":[180,392],"functional":[181],"gene":[182,445],"set":[183],"enrichment":[184],"histological":[186],"analyses":[187],"KRAS*-expressing":[189,263],"metastases,":[191],"we":[192],"uncovered":[194],"robust":[196],"adipogenesis":[197],"signature":[198],"abundance":[201],"lipid-rich":[203,278],"fibroblasts":[204,218,279],"angiogenesis":[206],"tumor":[209,274],"microenvironment.":[210],"co-culture":[213],"experiments":[214],"involving":[215],"embryonic":[217],"conditioned":[220],"media":[221],"from":[222],"primary":[224],"cell":[225,233],"lines":[226],"induced":[228],"their":[229],"differentiation":[230],"into":[231,356,468],"population":[234],"displaying":[235],"traits":[236],"both":[238,292],"adipocytes":[239],"fibroblasts,":[241],"aptly":[242],"'lipid-rich":[246],"fibroblasts.'":[247],"In":[248,336,389,455],"initial":[250],"segment":[251],"my":[253,460],"study,":[254],"I":[255,345,462],"elucidated":[257],"molecular":[259],"cells":[265],"lipo-fibrogenesis":[267],"shed":[270],"light":[271],"on":[272],"biological":[275,448,493],"role":[276,315],"facilitating":[281],"progression.":[284],"As":[285],"only":[286],"minority":[288],"cases":[290],"among":[291],"human":[293,436],"show":[298],"disease,":[302],"it":[303,438],"clear":[305],"genetic":[307],"events":[308,342],"beyond":[309],"activation":[311],"play":[312],"pivotal":[314],"Notably,":[319],"patients,":[320],"irrespective":[321],"mutations,":[324],"nearly":[327],"identical":[328],"lymph":[329],"node":[330],"approximately":[334],"40%.":[335],"order":[337],"explore":[339],"these":[340],"pro-metastasis":[341],"more":[343],"effectively,":[344],"propose":[346],"integration":[348],"telomerase":[352,387,484],"reverse":[353],"transcriptase":[354],"(LSL-Tert)":[355],"existing":[358],"iAP":[359,426,470],"Tp53.":[371],"introduced":[373,464],"modification":[374],"enables":[375],"us":[376],"replicate":[378,431],"telomere-based":[379,481],"crisis":[380,482],"genome":[382],"instability,":[383],"subsequently":[384],"followed":[385],"reactivation.":[388],"prior":[390],"studies":[391],"telomerase-inducible":[393],"models":[395],"prostate":[397],"cancer,":[398],"introduction":[400],"crisis-telomerase":[402],"sequences":[403],"led":[404],"development":[407],"cancer-relevant":[409],"genomic":[410,422],"aberrations":[411],"escalation":[414],"potential.":[417],"inclusion":[420],"instability":[423],"within":[424],"may":[428],"not":[429],"fully":[430],"intricacies":[433],"context,":[437],"does":[439],"provide":[440],"platform":[442],"identifying":[444],"alterations":[446],"transformations":[449],"associated":[450],"process.":[454],"second":[457],"phase":[458],"research,":[461],"human-like":[465],"telomere":[466],"dynamics":[467],"iTAP)":[475],"investigate":[477],"consequences":[479],"reactivation":[485],"unraveling":[490],"underlying":[492],"changes.":[494],"These":[495],"endeavors":[496],"hold":[497],"potential":[499],"expedite":[501],"discovery":[503],"novel":[505],"disease.":[511]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2025-10-10T00:00:00"}
