{"id":"https://openalex.org/W7208747661","doi":"https://doi.org/10.64898/2026.09.02.748398","title":"A CD109-SMURF2 Axis Diverts EGFR from Degradation to Sustain Oncogenic Signaling and Promote Squamous Cell Carcinoma Invasion and Stemness","display_name":"A CD109-SMURF2 Axis Diverts EGFR from Degradation to Sustain Oncogenic Signaling and Promote Squamous Cell Carcinoma Invasion and Stemness","publication_year":2026,"publication_date":"2026-09-03","ids":{"openalex":"https://openalex.org/W7208747661","doi":"https://doi.org/10.64898/2026.09.02.748398"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.02.748398","doi":"https://doi.org/10.64898/2026.09.02.748398","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.02.748398","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/03/2026.09.02.748398.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/03/2026.09.02.748398.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5006820489","display_name":"Tenzin Kungyal","orcid":"https://orcid.org/0000-0003-4827-0264","observed_orcids":["https://orcid.org/0000-0003-4827-0264"]},"institutions":[{"id":"https://openalex.org/I5023651","display_name":"McGill University","ror":"https://ror.org/01pxwe438","country_code":"CA","type":"education","lineage":["https://openalex.org/I5023651"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Tenzin Kungyal","raw_affiliation_strings":["Divisions of Plastic Surgery, and Surgical and Interventional Sciences, Department of Surgery, McGill University, Montreal, Quebec, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Divisions of Plastic Surgery, and Surgical and Interventional Sciences, Department of Surgery, McGill University, Montreal, Quebec, Canada","institution_ids":["https://openalex.org/I5023651"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000947361","display_name":"Amani Hassan","orcid":"https://orcid.org/0000-0002-7542-6976","observed_orcids":["https://orcid.org/0000-0002-7542-6976"]},"institutions":[{"id":"https://openalex.org/I5023651","display_name":"McGill University","ror":"https://ror.org/01pxwe438","country_code":"CA","type":"education","lineage":["https://openalex.org/I5023651"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Amani Hassan","raw_affiliation_strings":["Divisions of Plastic Surgery, and Surgical and Interventional Sciences, Department of Surgery, McGill University, Montreal, Quebec, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Divisions of Plastic Surgery, and Surgical and Interventional Sciences, Department of Surgery, McGill University, Montreal, Quebec, Canada","institution_ids":["https://openalex.org/I5023651"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036332797","display_name":"Kenneth W. Finnson","orcid":"https://orcid.org/0000-0003-2930-0595","observed_orcids":["https://orcid.org/0000-0003-2930-0595"]},"institutions":[{"id":"https://openalex.org/I5023651","display_name":"McGill University","ror":"https://ror.org/01pxwe438","country_code":"CA","type":"education","lineage":["https://openalex.org/I5023651"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Kenneth Finnson","raw_affiliation_strings":["Divisions of Plastic Surgery, and Surgical and Interventional Sciences, Department of Surgery, McGill University, Montreal, Quebec, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Divisions of Plastic Surgery, and Surgical and Interventional Sciences, Department of Surgery, McGill University, Montreal, Quebec, Canada","institution_ids":["https://openalex.org/I5023651"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5019595615","display_name":"Varsha Reddy Durgempudi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I5023651","display_name":"McGill University","ror":"https://ror.org/01pxwe438","country_code":"CA","type":"education","lineage":["https://openalex.org/I5023651"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Varsha Reddy Durgempudi","raw_affiliation_strings":["Divisions of Plastic Surgery, and Surgical and Interventional Sciences, Department of Surgery, McGill University, Montreal, Quebec, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Divisions of Plastic Surgery, and Surgical and Interventional Sciences, Department of Surgery, McGill University, Montreal, Quebec, Canada","institution_ids":["https://openalex.org/I5023651"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5029233463","display_name":"Anie Philip","orcid":"https://orcid.org/0000-0002-2533-1071","observed_orcids":["https://orcid.org/0000-0002-2533-1071"]},"institutions":[{"id":"https://openalex.org/I5023651","display_name":"McGill University","ror":"https://ror.org/01pxwe438","country_code":"CA","type":"education","lineage":["https://openalex.org/I5023651"]}],"countries":["CA"],"is_corresponding":true,"raw_author_name":"Anie Philip","raw_affiliation_strings":["Divisions of Dermatology and Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada","Divisions of Plastic Surgery, and Surgical and Interventional Sciences, Department of Surgery, McGill University, Montreal, Quebec, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Divisions of Dermatology and Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada","institution_ids":["https://openalex.org/I5023651"]},{"raw_affiliation_string":"Divisions of Plastic Surgery, and Surgical and Interventional Sciences, Department of Surgery, McGill University, Montreal, Quebec, Canada","institution_ids":["https://openalex.org/I5023651"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5029233463"],"corresponding_institution_ids":["https://openalex.org/I5023651"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"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":false,"primary_topic":{"id":"https://openalex.org/T10755","display_name":"HER2/EGFR in Cancer Research","score":0.8978999853134155,"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/T10755","display_name":"HER2/EGFR in Cancer Research","score":0.8978999853134155,"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/T10307","display_name":"Head and Neck Cancer Studies","score":0.0731000006198883,"subfield":{"id":"https://openalex.org/subfields/2733","display_name":"Otorhinolaryngology"},"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/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.003700000001117587,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"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/cd109","display_name":"CD109","score":1.0},{"id":"https://openalex.org/keywords/smurf2","display_name":"Smurf2","score":0.9950000047683716},{"id":"https://openalex.org/keywords/egfr","display_name":"EGFR","score":0.953000009059906},{"id":"https://openalex.org/keywords/head-and-neck-squamous-cell-carcinoma","display_name":"head and neck squamous cell carcinoma","score":0.9649999737739563},{"id":"https://openalex.org/keywords/protein-degradation","display_name":"protein degradation","score":0.5640000104904175},{"id":"https://openalex.org/keywords/egfr-phosphorylation","display_name":"EGFR phosphorylation","score":0.8059999942779541},{"id":"https://openalex.org/keywords/stat3-signaling","display_name":"STAT3 signaling","score":0.9490000009536743},{"id":"https://openalex.org/keywords/akt-signaling","display_name":"Akt signaling","score":0.9909999966621399},{"id":"https://openalex.org/keywords/erk-signaling","display_name":"ERK signaling","score":0.9990000128746033},{"id":"https://openalex.org/keywords/tumor-invasion","display_name":"tumor invasion","score":0.7289999723434448},{"id":"https://openalex.org/keywords/cancer-stemness","display_name":"cancer stemness","score":0.9129999876022339},{"id":"https://openalex.org/keywords/disease-free-survival","display_name":"disease-free survival","score":0.6570000052452087},{"id":"https://openalex.org/keywords/therapeutic-target","display_name":"therapeutic target","score":0.6439999938011169}],"concepts":[{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6617000102996826},{"id":"https://openalex.org/C2777506169","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"EGFR inhibitors","level":4,"score":0.6233999729156494},{"id":"https://openalex.org/C2779438470","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"Epidermal growth factor receptor","level":3,"score":0.576200008392334},{"id":"https://openalex.org/C134459356","wikidata":"https://www.wikidata.org/wiki/Q4274835","display_name":"Ubiquitin ligase","level":4,"score":0.5748000144958496},{"id":"https://openalex.org/C25602115","wikidata":"https://www.wikidata.org/wiki/Q407111","display_name":"Ubiquitin","level":3,"score":0.5450999736785889},{"id":"https://openalex.org/C2776833033","wikidata":"https://www.wikidata.org/wiki/Q1783924","display_name":"Head and neck squamous-cell carcinoma","level":4,"score":0.5103999972343445},{"id":"https://openalex.org/C204232928","wikidata":"https://www.wikidata.org/wiki/Q899285","display_name":"Immunohistochemistry","level":2,"score":0.4323999881744385},{"id":"https://openalex.org/C179185449","wikidata":"https://www.wikidata.org/wiki/Q219699","display_name":"Suppressor","level":3,"score":0.4189000129699707},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.41780000925064087},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.4059000015258789},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4058000147342682},{"id":"https://openalex.org/C62112901","wikidata":"https://www.wikidata.org/wiki/Q189159","display_name":"Cell growth","level":2,"score":0.38769999146461487},{"id":"https://openalex.org/C2107291","wikidata":"https://www.wikidata.org/wiki/Q14886885","display_name":"Mediator","level":2,"score":0.3869999945163727},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3790000081062317},{"id":"https://openalex.org/C2776192174","wikidata":"https://www.wikidata.org/wiki/Q18028978","display_name":"Mdm2","level":3,"score":0.3709000051021576},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.3614000082015991},{"id":"https://openalex.org/C170240278","wikidata":"https://www.wikidata.org/wiki/Q17928773","display_name":"FOXM1","level":4,"score":0.3596000075340271},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3441999852657318},{"id":"https://openalex.org/C86339819","wikidata":"https://www.wikidata.org/wiki/Q407384","display_name":"Transcription factor","level":3,"score":0.33329999446868896},{"id":"https://openalex.org/C3019992690","wikidata":"https://www.wikidata.org/wiki/Q92767510","display_name":"Basal cell","level":2,"score":0.31700000166893005},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.31679999828338623},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.30730000138282776},{"id":"https://openalex.org/C555283112","wikidata":"https://www.wikidata.org/wiki/Q1637543","display_name":"Carcinogenesis","level":3,"score":0.30160000920295715},{"id":"https://openalex.org/C115456853","wikidata":"https://www.wikidata.org/wiki/Q17917132","display_name":"ERBB3","level":4,"score":0.29739999771118164},{"id":"https://openalex.org/C2779998722","wikidata":"https://www.wikidata.org/wiki/Q420296","display_name":"Cetuximab","level":4,"score":0.2816999852657318},{"id":"https://openalex.org/C150555746","wikidata":"https://www.wikidata.org/wiki/Q210973","display_name":"Cell signaling","level":3,"score":0.2809999883174896},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.28040000796318054},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.2800000011920929},{"id":"https://openalex.org/C116227048","wikidata":"https://www.wikidata.org/wiki/Q18021243","display_name":"Cyclin-dependent kinase 8","level":4,"score":0.27810001373291016},{"id":"https://openalex.org/C2994460389","wikidata":"https://www.wikidata.org/wiki/Q681817","display_name":"Epidermoid carcinoma","level":3,"score":0.25920000672340393},{"id":"https://openalex.org/C88498014","wikidata":"https://www.wikidata.org/wiki/Q14859918","display_name":"Hedgehog signaling pathway","level":3,"score":0.25760000944137573},{"id":"https://openalex.org/C2781230642","wikidata":"https://www.wikidata.org/wiki/Q492646","display_name":"Targeted therapy","level":3,"score":0.2567000091075897},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.250900000333786}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.02.748398","doi":"https://doi.org/10.64898/2026.09.02.748398","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.02.748398","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/03/2026.09.02.748398.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.02.748398","doi":"https://doi.org/10.64898/2026.09.02.748398","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.02.748398","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/03/2026.09.02.748398.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9537000060081482}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7208747661.pdf","grobid_xml":"https://content.openalex.org/works/W7208747661.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4288435843","https://openalex.org/W7165657685","https://openalex.org/W4393093616","https://openalex.org/W7046414123","https://openalex.org/W1972316552","https://openalex.org/W2800969015","https://openalex.org/W3033410235","https://openalex.org/W2988318212","https://openalex.org/W2065691207","https://openalex.org/W2994852154"],"abstract_inverted_index":{"Abstract":[0],"Squamous":[1],"cell":[2],"carcinoma":[3],"(SCC)":[4],"remains":[5],"difficult":[6],"to":[7],"treat,":[8],"particularly":[9],"in":[10,38,43,59,65,102,123,150,171,185,230],"recurrent":[11],"or":[12],"metastatic":[13],"disease.":[14],"Although":[15],"EGFR":[16,44,110,114,157,160,169,198,202],"signaling":[17],"is":[18,57],"a":[19,33,134,172,194,223],"well-established":[20],"driver":[21],"of":[22,136],"SCC":[23,63,151,186],"pathogenesis,":[24],"mechanisms":[25,48],"regulating":[26],"its":[27,47],"activity":[28],"remain":[29,49],"incompletely":[30],"understood.":[31],"CD109,":[32,91],"GPI-anchored":[34],"glycoprotein":[35],"frequently":[36],"overexpressed":[37],"SCC,":[39],"has":[40],"been":[41],"implicated":[42],"signaling,":[45],"but":[46],"poorly":[50],"defined.":[51],"Here,":[52],"we":[53],"show":[54],"that":[55,154],"CD109":[56,107,140,192],"elevated":[58],"head":[60],"and":[61,70,82,93,117,127,147,183],"neck":[62],"(HNSCC)":[64],"the":[66,163,176,219],"TCGA":[67],"PanCancer":[68,80],"Atlas":[69],"significantly":[71],"correlates":[72],"with":[73,139,162,225],"reduced":[74],"disease-free":[75],"survival.":[76],"Integrative":[77],"transcriptomic":[78],"(TCGA":[79],"Atlas)":[81],"proteomic":[83],"(LinkedOmics)":[84],"analyses":[85],"revealed":[86],"strong":[87],"positive":[88],"correlations":[89],"between":[90],"EGFR,":[92],"SMURF2.":[94],"These":[95],"findings":[96,190],"were":[97],"further":[98],"validated":[99],"by":[100,158,200],"immunohistochemistry":[101],"HNSCC":[103],"patient":[104],"samples.":[105],"Mechanistically,":[106],"overexpression":[108],"impaired":[109],"degradation,":[111],"suppressed":[112],"degradation-associated":[113],"pY1045":[115],"phosphorylation,":[116,121],"enhanced":[118],"signaling-associated":[119],"pY1068":[120],"resulting":[122],"increased":[124],"STAT3,":[125],"AKT,":[126],"ERK":[128],"signaling.":[129,212],"We":[130],"identify":[131,191],"SMURF2":[132,145,155],"as":[133,193,222],"mediator":[135],"these":[137,189],"effects,":[138],"promoting":[141],"EGFR-SMURF2":[142],"complex":[143],"formation.":[144],"gain-":[146],"loss-of-function":[148],"studies":[149],"cells,":[152],"demonstrated":[153],"stabilizes":[156],"reducing":[159],"interaction":[161],"ubiquitin":[164],"ligase":[165],"c-Cbl,":[166],"thereby":[167],"limiting":[168],"turnover":[170],"CD109-dependent":[173],"manner.":[174],"Functionally,":[175],"CD109-SMURF2-EGFR":[177],"axis":[178,221],"promotes":[179],"EGF-induced":[180],"stemness,":[181],"invasion,":[182],"proliferation":[184],"cells.":[187],"Together,":[188],"molecular":[195],"switch":[196],"controlling":[197],"fate":[199],"redirecting":[201],"from":[203],"c-Cbl-mediated":[204],"degradation":[205],"toward":[206],"SMURF2-":[207],"dependent":[208],"stabilization,":[209],"sustaining":[210],"oncogenic":[211],"This":[213],"previously":[214],"unrecognized":[215],"regulatory":[216],"pathway":[217],"reveals":[218],"CD109-SMURF2":[220],"vulnerability":[224],"potential":[226],"for":[227],"targeted":[228],"intervention":[229],"EGFR-driven":[231],"SCCs.":[232]},"counts_by_year":[],"updated_date":"2026-10-28T10:33:24.094632","created_date":"2026-09-05T00:00:00"}
