Mechanism underlying the FGFR2 control of HIF-mediated hypoxic response in prostate cancer : 전립선 암에서 FGFR2에 의한 HIF 저산소 반응의 조절 기전에 관한 연구

Cited 0 time in Web of Science Cited 0 time in Scopus


의과대학 의과학과
Issue Date
서울대학교 대학원
학위논문 (석사)-- 서울대학교 대학원 : 의과대학 의과학과, 2018. 8. 박종완.
Hypoxia-inducible factors (HIFs) are the transcription factors that aid cancer cells to survive under hypoxic challenges and to spread out via invasion and metastasis. Therefore, HIF is currently regarded as a compelling target for cancer therapy. The cell surface receptor FGFR has been known to enhance the synthesis of HIF through the receptor signaling pathway. Recent studies have shown that FGFR is also present in the nucleus, suggesting that FGFR plays additional roles in gene regulation. Yet, the roles of nuclear FGFR are not uncovered. In this study, I revealed that FGFR2, a member of the FGFR family, functions to modulate the HIF-driven gene expression. Using the TGCA database, I found that downregulation of FGFR2 is associated with poor prognosis in prostate cancer. FGFR2 is downregulated in primary and metastatic tissues of prostate cancer compared to normal prostate tissues. A gene set enrichment analysis showed that metastasis-related genes and hypoxia-related genes are associated with a low expression of FGFR2 in prostate cancer. Thus, I tested the possibility that FGFR2 negatively regulates the hypoxia-triggered metastasis of prostate cancer. Consequently, FGFR2 was shown to control migration and invasion of prostate cancer cells under hypoxia by inhibiting the HIF-driven gene expression. FGFR2 and HIF-1/2α proteins co-localized in the nucleus and interacted with each other under hypoxic conditions. FGFR2 bound to the CAD domain of HIF-1α and this binding blocked the recruitment of a coactivator p300 by HIF-1α, resulting in repression of HIF target genes. Based on these results, I propose a novel function of FGFR2 in controlling HIF-mediated hypoxic responses. In prostate cancer with hypoxic zones, FGFR2 may act as a metastasis suppressor.
Files in This Item:
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Theses (Master's Degree_의과학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.