Regulation of ER-beta Signaling in Carcinogenesis

ER-β 信号传导在癌发生过程中的调节

基本信息

  • 批准号:
    10092967
  • 负责人:
  • 金额:
    $ 48.43万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-02-01 至 2022-01-31
  • 项目状态:
    已结题

项目摘要

Estrogen receptor (ER)β exhibits an antitumor activity in multiple cancer types in both tumor-intrinsic and -extrinsic manners. However, little is known as to how such activity can be harnessed with high efficacy and precision, nor is it clear which host cell type(s) mediates the tumor-extrinsic function of ERβ. These major knowledge gaps hamper efforts to unleash ERβ antitumor activity for cancer therapies. We recently discovered a phosphotyrosine-dependent signaling axis that controls ERβ antitumor activity. Furthermore, using a novel knockin mouse model, we found that this phosphotyrosine switch plays a significant role in host cells to promote antitumor immunity. Our central hypothesis is that this ERβ-centered signaling axis provides a previously unrecognized molecular handle for mobilizing tumor-extrinsic antitumor activity of ERβ in immune cells. Armed with genetic and pharmacological tools that both specifically target this signaling circuit, our multi-PI team will validate this novel hypothesis through three Specific Aims. First, we will identify the exact immune cell type(s) that mediates tumor-extrinsic ERβ signaling in antitumor immunity (Aim 1). We will then delineate the upstream regulators and downstream target genes of ERβ signaling in immune cells (Aim 2). Lastly, we will assess the anticancer therapeutic potential of targeting this ERβ signaling axis to boost current cancer immunotherapies. Findings from these experiments will shed light on a previously under-appreciated signaling pathway governing tumor-immune cell interactions in the tumor microenvironment. As immunotherapies are becoming an important pillar of cancer therapy, the proposed study will help improve clinical outcomes and efficacy of immunotherapy for larger numbers of cancer patients.
雌激素受体(ER)β在多种肿瘤类型中均表现出抗肿瘤活性

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)
A Phosphotyrosine Switch in Estrogen Receptor β Is Required for Mouse Ovarian Function.
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Tyler J. Curiel其他文献

ESTABLISHMENT OF A DOUBLE-HUMANIZED MOUSE MODEL USING PATIENT-DERIVED XENOGRAFT BLADDER CANCER TUMOR CELL LINE AND HUMAN γδ T-CELLS
  • DOI:
    10.1016/j.urolonc.2024.01.171
  • 发表时间:
    2024-03-01
  • 期刊:
  • 影响因子:
  • 作者:
    Shaun Trecarten;Robert S. Svatek;Niannian Ji;Zhen-Ju Shu;Tyler J. Curiel;Neelam Mukherjee;Jamie Furman
  • 通讯作者:
    Jamie Furman
PD48-06 2 YEAR CLINICAL AND IMMUNOLOGIC OUTCOMES OF INTRADERMAL BCG PRIMING PRIOR TO INTRAVESICAL INDUCTION IMMUNOTHERAPY FOR HIGH RISK NON-MUSCLE INVASIVE BLADDER CANCER
  • DOI:
    10.1016/j.juro.2017.02.2354
  • 发表时间:
    2017-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Niannan Ji;Edwin E. Morales;Neelam Mukherjee;Vincent Hurez;Tyler J. Curiel;Getahun Abate;Daniel F. Hoft;Robert S. Svatek
  • 通讯作者:
    Robert S. Svatek
60: Oral rapamycin prevents carcinogen-induced dermal carcinogenesis through immune mechanisms
  • DOI:
    10.1016/j.cyto.2013.06.063
  • 发表时间:
    2013-09-01
  • 期刊:
  • 影响因子:
  • 作者:
    Vinh Dao;Vincent Hurez;Sri Lakshmi Pandeswara;Lishi Sun;Aijie Liu;Paul Hasty;Dave Sharp;Tyler J. Curiel
  • 通讯作者:
    Tyler J. Curiel

Tyler J. Curiel的其他文献

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{{ truncateString('Tyler J. Curiel', 18)}}的其他基金

Bladder cancer PD-L1 control of homologous recombination: Basic mechanisms applied to novel treatments
膀胱癌 PD-L1 对同源重组的控制:应用于新疗法的基本机制
  • 批准号:
    10467877
  • 财政年份:
    2022
  • 资助金额:
    $ 48.43万
  • 项目类别:
Bladder cancer PD-L1 control of homologous recombination: Basic mechanisms applied to novel treatments
膀胱癌 PD-L1 对同源重组的控制:应用于新疗法的基本机制
  • 批准号:
    10688261
  • 财政年份:
    2022
  • 资助金额:
    $ 48.43万
  • 项目类别:
(PQ2) PD-L1/PD-1 signals in aged hosts undergoing cancer immunotherapy
(PQ2) 接受癌症免疫治疗的老年宿主体内的 PD-L1/PD-1 信号
  • 批准号:
    9788318
  • 财政年份:
    2018
  • 资助金额:
    $ 48.43万
  • 项目类别:
(PQ2) PD-L1/PD-1 signals in aged hosts undergoing cancer immunotherapy
(PQ2) 接受癌症免疫治疗的老年宿主体内的 PD-L1/PD-1 信号
  • 批准号:
    10381324
  • 财政年份:
    2018
  • 资助金额:
    $ 48.43万
  • 项目类别:
(PQ2) PD-L1/PD-1 signals in aged hosts undergoing cancer immunotherapy
(PQ2) 接受癌症免疫治疗的老年宿主体内的 PD-L1/PD-1 信号
  • 批准号:
    10475260
  • 财政年份:
    2018
  • 资助金额:
    $ 48.43万
  • 项目类别:
(PQ2) PD-L1/PD-1 signals in aged hosts undergoing cancer immunotherapy
(PQ2) 接受癌症免疫治疗的老年宿主体内的 PD-L1/PD-1 信号
  • 批准号:
    10247570
  • 财政年份:
    2018
  • 资助金额:
    $ 48.43万
  • 项目类别:
(PQ#3) Novel tumor intrinsic PD-L1 signals direct tumor immune cell infiltration
(PQ
  • 批准号:
    9926828
  • 财政年份:
    2017
  • 资助金额:
    $ 48.43万
  • 项目类别:
(PQ#3) Novel tumor intrinsic PD-L1 signals direct tumor immune cell infiltration
(PQ
  • 批准号:
    9307468
  • 财政年份:
    2017
  • 资助金额:
    $ 48.43万
  • 项目类别:
SENIOR LEADERSHIP
高层领导
  • 批准号:
    8709459
  • 财政年份:
    2013
  • 资助金额:
    $ 48.43万
  • 项目类别:
Immune aspects of mTOR inhibition for cancer prevention (PQ5)
mTOR 抑制的免疫方面预防癌症 (PQ5)
  • 批准号:
    8538910
  • 财政年份:
    2012
  • 资助金额:
    $ 48.43万
  • 项目类别:

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