000000469 001__ 469
000000469 005__ 20260306074621.0
000000469 0247_ $$2DOI$$a10.6083/M4862DDG
000000469 037__ $$aETD
000000469 245__ $$aRole of Smad4 loss in head and neck squamous cell carcinoma
000000469 260__ $$bOregon Health and Science University
000000469 269__ $$a2008
000000469 336__ $$aDissertation
000000469 502__ $$bPh.D.
000000469 520__ $$aHead and neck squamous cell carcinoma (HNSCC) remains a major malignancy with poor improvement in outcomes over the past two decades. This work identifies Smad4 loss as a causal driver of HNSCC development. Conditional deletion of Smad4 in mouse head and neck epithelia led to spontaneous HNSCC accompanied by genomic instability, reduced expression of Fanconi anemia/Brca pathway genes, and heightened inflammation marked by elevated TGFβ1‑dependent cytokines. Smad4-deficient keratinocyte stem cells also displayed abnormal proliferation and retained multipotency. Together, these findings show that Smad4 loss promotes HNSCC through combined effects on genomic integrity, inflammatory signaling, and stem cell dysregulation.
000000469 540__ $$fCC BY
000000469 542__ $$fIn copyright - single owner
000000469 650__ $$aCarcinoma, Squamous Cell$$016128
000000469 650__ $$aSmad4 Protein$$037054
000000469 650__ $$aGenomic Instability$$035232
000000469 650__ $$aTransforming Growth Factor beta$$028969
000000469 650__ $$aFanconi Anemia$$018886
000000469 650__ $$aHead and Neck Neoplasms$$019866
000000469 650__ $$aSquamous Cell Carcinoma of Head and Neck$$012663
000000469 691__ $$aSchool of Medicine$$041369
000000469 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399
000000469 7001_ $$aBornstein, Sophia$$uOregon Health and Science University$$041354
000000469 7201_ $$aWang, Xiao-Jing$$uOregon Health and Science University$$041354$$7Personal$$eMentor
000000469 8564_ $$9ba84e642-06cf-40d0-83e1-cb41f9ea2eb4$$s1990773$$uhttps://digitalcollections.ohsu.edu/record/469/files/470_etd.pdf$$ePublic$$2109aeaec45e7dba9849fbc86ca6518fd$$31
000000469 905__ $$a/rest/prod/n2/96/wz/12/n296wz12m
000000469 909CO $$ooai:digitalcollections.ohsu.edu:469$$pstudent-work
000000469 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000469 980__ $$aTheses and Dissertations