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SUMOylated Etv1 Establishes Cancer Stem Cells That Support Non-Stem Cancer Cells Tumorigenesis
SUMOylated Etv1 Establishes Cancer Stem Cells That Support Non-Stem Cancer Cells Tumorigenesis
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202102955
- ISBN
- 9798286433650
- DDC
- 616.99
- 저자명
- Li, Zhijie.
- 서명/저자
- SUMOylated Etv1 Establishes Cancer Stem Cells That Support Non-Stem Cancer Cells Tumorigenesis
- 발행사항
- [Sl] : The University of Iowa, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 151 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Weigel, Ronald.
- 학위논문주기
- Thesis (Ph.D.)--The University of Iowa, 2025.
- 초록/해제
- 요약The Small Ubiquitin-like Modifier (SUMO) pathway serves as a post-translational regulatory mechanism involved in the maintenance and self-renewal of cancer stem cells/tumor-initiating cells (CSCs/TICs). In this study, we found that SUMO inhibition through genetic and pharmacologic approaches represses mammary oncogenesis and inhibits the function of CSCs. In contrast, SUMO inhibition did not affect the growth or mammosphere formation of normal mammary stem cells, suggesting SUMO-sensitive mechanisms are specific for maintaining the oncogenic CSC/TIC population. Transcriptomic analysis indicates ETS Translocation Variant 1, encoded by Etv1 gene, acts as a SUMO-sensitive transcription factor that drives mammary oncogenesis and cancer progression. Inhibition of SUMOylation resulted in a significant reduction in proliferation and colony formation in vitro and completely blocked the formation of flank xenografts in vivo. Expression of a SUMO-resistant Etv1 protein rescued in vitro growth effects, while the SUMO mimetic Etv1 protein had no effect on restoring proliferation. On the other hand, in vivo xenograft assays demonstrated that SUMO mimetic Etv1 protein efficiently induced tumor formation, whereas SUMO-resistant Etv1 protein was unable to rescue tumorigenesis. Bulk RNA-seq and ChIP-seq analyses revealed distinct gene signatures between SUMO-conjugated Etv1 in stem-like cells and SUMO-unconjugated Etv1 in proliferative, non-tumorigenic cells. Furthermore, we determined that stem-like cells could induce the proliferation of non-stem cells in tumorgenesis. Therefore, we conclude Etv1 acts as a SUMO-sensitive transcription factor that drives a stem cell phenotype necessary for mammary oncogenesis and tumorigenesis, providing potential targets for developing new therapeutic strategies.
- 일반주제명
- Oncology
- 일반주제명
- Genetics
- 일반주제명
- Molecular biology
- 일반주제명
- Biomedical engineering
- 키워드
- Stem cells
- 키워드
- Sumoylation
- 키워드
- Transcription
- 키워드
- Tumorigenesis
- 기타저자
- The University of Iowa Biomedical Science
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008260126s2025 us c eng d■001000017356574
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■006m o d
■007cr#unu||||||||
■020 ▼a9798286433650
■035 ▼a(MiAaPQ)AAI31768997
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.99
■1001 ▼aLi, Zhijie.
■24510▼aSUMOylated Etv1 Establishes Cancer Stem Cells That Support Non-Stem Cancer Cells Tumorigenesis
■260 ▼a[Sl]▼bThe University of Iowa▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a151 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Weigel, Ronald.
■5021 ▼aThesis (Ph.D.)--The University of Iowa, 2025.
■520 ▼aThe Small Ubiquitin-like Modifier (SUMO) pathway serves as a post-translational regulatory mechanism involved in the maintenance and self-renewal of cancer stem cells/tumor-initiating cells (CSCs/TICs). In this study, we found that SUMO inhibition through genetic and pharmacologic approaches represses mammary oncogenesis and inhibits the function of CSCs. In contrast, SUMO inhibition did not affect the growth or mammosphere formation of normal mammary stem cells, suggesting SUMO-sensitive mechanisms are specific for maintaining the oncogenic CSC/TIC population. Transcriptomic analysis indicates ETS Translocation Variant 1, encoded by Etv1 gene, acts as a SUMO-sensitive transcription factor that drives mammary oncogenesis and cancer progression. Inhibition of SUMOylation resulted in a significant reduction in proliferation and colony formation in vitro and completely blocked the formation of flank xenografts in vivo. Expression of a SUMO-resistant Etv1 protein rescued in vitro growth effects, while the SUMO mimetic Etv1 protein had no effect on restoring proliferation. On the other hand, in vivo xenograft assays demonstrated that SUMO mimetic Etv1 protein efficiently induced tumor formation, whereas SUMO-resistant Etv1 protein was unable to rescue tumorigenesis. Bulk RNA-seq and ChIP-seq analyses revealed distinct gene signatures between SUMO-conjugated Etv1 in stem-like cells and SUMO-unconjugated Etv1 in proliferative, non-tumorigenic cells. Furthermore, we determined that stem-like cells could induce the proliferation of non-stem cells in tumorgenesis. Therefore, we conclude Etv1 acts as a SUMO-sensitive transcription factor that drives a stem cell phenotype necessary for mammary oncogenesis and tumorigenesis, providing potential targets for developing new therapeutic strategies.
■590 ▼aSchool code: 0096.
■650 4▼aOncology
■650 4▼aGenetics
■650 4▼aMolecular biology
■650 4▼aBiomedical engineering
■653 ▼aMammary oncogenesis
■653 ▼aStem cells
■653 ▼aSumoylation
■653 ▼aTranscription
■653 ▼aTumorigenesis
■690 ▼a0992
■690 ▼a0369
■690 ▼a0307
■690 ▼a0541
■71020▼aThe University of Iowa▼bBiomedical Science.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0096
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17356574▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
