000000417 001__ 417
000000417 005__ 20260305084740.0
000000417 0247_ $$2DOI$$a10.6083/M4028PG3
000000417 037__ $$aETD
000000417 245__ $$aThe role of keratinocyte-specific Smad2 loss in skin squamous cell carcinomas
000000417 260__ $$bOregon Health and Science University
000000417 269__ $$a2008
000000417 336__ $$aDissertation
000000417 502__ $$bPh.D.
000000417 520__ $$aSmad2 and Smad4, but not Smad3, are frequently lost in human skin squamous cell carcinomas (SCCs. Keratinocyte‑specific Smad2 knockout mice showed accelerated tumor formation, poor differentiation, and epithelial–mesenchymal transition (EMT), driven by increased Snail expression. Smad2 loss enhanced Smad3/Smad4‑mediated Snail transcription. Both Smad2‑ and Smad4‑deficient tumors exhibited increased angiogenesis, but through distinct pathways: Smad4 loss elevated VEGF and TGFβ‑dependent signaling, whereas Smad2 loss increased hepatocyte growth factor (HGF). Promoter studies showed Smad2 normally represses HGF while Smad4 activates it. Overall, Smad2 and Smad4 deletions promote EMT and angiogenesis through complementary mechanisms that drive skin carcinogenesis.
000000417 540__ $$fCC BY
000000417 542__ $$fIn copyright - single owner
000000417 650__ $$aCarcinoma, Squamous Cell$$016128
000000417 650__ $$aTransforming Growth Factor beta$$028969
000000417 650__ $$aSkin Neoplasms$$026054
000000417 650__ $$aSmad Proteins$$037003
000000417 650__ $$aHepatocyte Growth Factor$$029793
000000417 650__ $$aVascular Endothelial Growth Factor A$$035189
000000417 650__ $$aCarcinogenesis$$040251
000000417 650__ $$aMice, Knockout$$030736
000000417 650__ $$aKeratinocytes$$028512
000000417 691__ $$aSchool of Medicine$$041369
000000417 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399
000000417 7001_ $$aHoot, Kristina$$uOregon Health and Science University$$041354
000000417 7201_ $$aWang, Xiao-Jing$$uOregon Health and Science University$$041354$$7Personal$$eMentor
000000417 7201_ $$aPillers, De-Ann$$uUniversity of Illinois Chicago$$7Personal$$eMentor
000000417 8564_ $$9605adaa4-b2c0-4914-a407-7f9663498e1a$$s3337736$$uhttps://digitalcollections.ohsu.edu/record/417/files/418_etd.pdf$$ePublic$$223481b4da644436536e3bd430585d874$$31
000000417 905__ $$a/rest/prod/n8/70/zq/85/n870zq85d
000000417 909CO $$ooai:digitalcollections.ohsu.edu:417$$pstudent-work
000000417 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000417 980__ $$aTheses and Dissertations