학술행사/세미나 안내 및 신청
Reciprocal interactions of androgen and IGF1 signaling pathways between prostate cancer stem cells and niches
연사
김원경 박사 (City of Hope, Cancer Center and Beckman Research Institute, Duarte, CA, USA)
세미나개최일
2024. 01. 09. 오후 4시
작성자
이상국
작성일
2024-01-04
조회
389
RECIPROCAL INTERACTIONS OF ANDROGEN AND IGF1 SIGNALING PATHWAYS BETWEEN PROSTATE CANCER STEM CELLS AND NICHES
Abstract: Unlike other human malignancies, androgen-mediated androgen receptor (AR) signaling plays an essential role in prostate tumorigenesis. Additionally, the interactions between AR signaling and different growth factors directly regulate prostate cell cycle, differentiation, apoptosis, and proliferation, promoting prostate cancer (PCa) initiation and progression. Among these growth factors, the insulin-like growth factor 1 (IGF1)-mediated signaling pathway ise of the most prominent pathways in prostate tumorigenesis. Substantial evidence from clinical and experimental studies further showed IGF1 signaling activation supporting both androgen-dependent and -independent PCa growth. However, the regulatory mechanisms underlying androgen and IGF1-mediated signaling pathways to initiate prostatecogenesis and PCa development remain elusive. Specifically, how androgen/AR action regulates IGF1 signaling pathway through epithelia-stroma interactions to induce hormone refractoriness and PCa progression during androgen deprivation therapies is also unknown. Here, a dynamic role of androgen/AR in regulation of IGF1 signaling through both augmenting the IGF1R transcription in prostatic basal epithelial progenitors and attenuating IGF binding protein 3-mediated neutralizing IGF1 to increase IGF1 secretion in prostatic stromal cells was identified. These new findings suggest the future preventative and therapeutic strategies for PCa by co-targetingcogenic effects of AR and IGF1 in both PCa cells and stromal niches.
Abstract: Unlike other human malignancies, androgen-mediated androgen receptor (AR) signaling plays an essential role in prostate tumorigenesis. Additionally, the interactions between AR signaling and different growth factors directly regulate prostate cell cycle, differentiation, apoptosis, and proliferation, promoting prostate cancer (PCa) initiation and progression. Among these growth factors, the insulin-like growth factor 1 (IGF1)-mediated signaling pathway ise of the most prominent pathways in prostate tumorigenesis. Substantial evidence from clinical and experimental studies further showed IGF1 signaling activation supporting both androgen-dependent and -independent PCa growth. However, the regulatory mechanisms underlying androgen and IGF1-mediated signaling pathways to initiate prostatecogenesis and PCa development remain elusive. Specifically, how androgen/AR action regulates IGF1 signaling pathway through epithelia-stroma interactions to induce hormone refractoriness and PCa progression during androgen deprivation therapies is also unknown. Here, a dynamic role of androgen/AR in regulation of IGF1 signaling through both augmenting the IGF1R transcription in prostatic basal epithelial progenitors and attenuating IGF binding protein 3-mediated neutralizing IGF1 to increase IGF1 secretion in prostatic stromal cells was identified. These new findings suggest the future preventative and therapeutic strategies for PCa by co-targetingcogenic effects of AR and IGF1 in both PCa cells and stromal niches.
