Determining the Mechanism of C-Raf Driven Metastasis- [electronic resource]
Determining the Mechanism of C-Raf Driven Metastasis- [electronic resource]
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214101241
- ISBN
- 9798379709914
- DDC
- 616.99
- 저자명
- Ta, Lisa Hieu.
- 서명/저자
- Determining the Mechanism of C-Raf Driven Metastasis - [electronic resource]
- 발행사항
- [S.l.]: : University of California, Los Angeles., 2023
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2023
- 형태사항
- 1 online resource(112 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
- 주기사항
- Advisor: Witte, Owen N. .
- 학위논문주기
- Thesis (Ph.D.)--University of California, Los Angeles, 2023.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 요약Mutated Ras and Raf kinases are well-known to promote cancer metastasis via flux through the Ras/Raf/MEK/ERK (MAPK) pathway. A role for non-mutated Raf in metastasis is also emerging, but the driving mechanisms remain unclear. Elevated expression of any of the three wildtype Raf family members (C, A or B) can drive metastasis. Here, we utilized an in vivo model to show that wildtype C-Raf overexpression can promote metastasis of immortalized prostate cells in a gene dosage dependent manner. Analysis of the transcriptomic and phospho-proteomic landscape indicated that C-Raf driven metastasis is accompanied by upregulated MAPK signaling. Use of C-Raf mutants demonstrated that the dimerization domain, but not its kinase activity is essential for metastasis. Endogenous Raf monomer knockouts revealed C-Raf's ability to form heterodimers with A-Raf and B-Raf are important for promoting metastasis. Taken together, these data identify wildtype C-Raf heterodimer signaling as a potential target for treating metastatic disease.
- 일반주제명
- Oncology.
- 일반주제명
- Molecular biology.
- 일반주제명
- Biochemistry.
- 키워드
- Dimerization
- 키워드
- Kinase
- 키워드
- Metastasis
- 키워드
- Wild-type
- 기타저자
- University of California, Los Angeles Molecular and Medical Pharmacology 0639
- 기본자료저록
- Dissertations Abstracts International. 84-12B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.