Basal Cell Polarity Proteins in Normal Tissue Homeostasis and Cancer

正常组织稳态和癌症中的基底细胞极性蛋白

基本信息

  • 批准号:
    10667590
  • 负责人:
  • 金额:
    $ 39.45万
  • 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:
    2019-06-07 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

Normal tissue homeostasis is maintained by adult stem and progenitor cells that use cell intrinsic mechanisms and information from their microenvironment to execute a very complex specialized type of mitosis known as asymmetric cell division. Two resulting from this division daughter cells acquire different cell fates. While one cell continues proliferation, another daughter cell withdraws from the stem cell niche, remodels its intercellular interactions and starts a program which ultimately leads to the cell cycle withdrawal and differentiation. This process ensures that only the necessary number of cells is produced at any given time and the cell death and depletion in each tissue is balanced by the birth of new cells. Defective asymmetric cell division can result in the failure of normal tissue homeostasis and birth of cancer stem cells, which cannot produce daughters that can properly withdraw from the cell cycle and differentiate. While asymmetric cell division plays a pivotal role in tissue homeostasis, little is known about its mechanisms in mammalian organisms. Studies in model organisms revealed critical role of intercellular interactions and apical-basal cell polarity in regulation of asymmetric cell division. In Drosophila, basal cell polarity gene lethal giant larvae (lgl) was identified as an important regulator of asymmetric cell division, and mutations in lgl result in overproduction of dividing stem cells and development of cancer. Mammalian genomes contain two lgl orthologs Llgl1 and Llgl2. While previous studies of LLGL1 and LLGL2 in cancer cell lines indicated their potential role as tumor suppressors, genetic analysis of these genes in mice was complicated by the genetic redundancy and lethality of Llgl mutants. We have now generated conditional, tissue specific Llgl1/2 double knockout mice. Our preliminary experiments revealed tumor-suppressive function of Llgl1/2 in skin squamous cell carcinoma. In this grant, we propose to use our mutant animals, primary cell cultures and in utero lentiviral transduction of skin epidermis to reveal the role and molecular mechanisms of Llgl gene family in stem and progenitor cells during normal tissue homeostasis and cancer. These studies will help to understand the mechanisms of mammalian stem and progenitor cells self-renewal and differentiation and the role of these mechanisms in cancer.
正常的组织稳态由成体干细胞和祖细胞维持, 机制和信息来执行非常复杂的专用类型 有丝分裂称为不对称细胞分裂。由此产生的两个子细胞获得 不同的细胞命运当一个细胞继续增殖时,另一个子细胞从干细胞中退出 细胞龛,重塑其细胞间的相互作用,并启动一个程序,最终导致细胞 周期退出和分化。这个过程确保了只有必要数量的细胞被 在任何给定的时间产生,每个组织中的细胞死亡和消耗都由 新的细胞有缺陷的不对称细胞分裂可导致正常组织稳态的失败, 癌症干细胞的诞生,它不能产生可以正确退出细胞的子细胞 循环和分化。虽然不对称细胞分裂在组织稳态中发挥着关键作用,但很少 已知其在哺乳动物中的作用机制。对模式生物的研究表明, 细胞间相互作用和顶基细胞极性在调节细胞不对称分裂中的作用。 在果蝇中,基底细胞极性基因致死性巨幼虫(lgl)被确定为一个重要的调节因子 不对称的细胞分裂,lgl的突变导致分裂干细胞的过度产生, 癌症的发展。哺乳动物基因组含有两个lgl直系同源物Llgll和Llgl2。虽然以前的 LLGL 1和LLGL 2在癌细胞系中的研究表明它们作为肿瘤抑制剂的潜在作用, 小鼠中这些基因的遗传分析由于Llgl的遗传冗余和致死性而变得复杂 变种人我们现在已经产生了条件性的、组织特异性的Llgl1/2双敲除小鼠。我们 初步实验显示Llgl 1/2在皮肤鳞状细胞中具有抑瘤功能, carcinoma.在这项资助中,我们建议使用我们的突变动物,原代细胞培养和子宫内 慢病毒转导皮肤表皮揭示Llgl基因家族的作用和分子机制 在正常组织稳态和癌症期间的干细胞和祖细胞中。这些研究将有助于 了解哺乳动物干细胞和祖细胞自我更新和分化的机制 以及这些机制在癌症中的作用。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
YAP1 and its fusion proteins in cancer initiation, progression and therapeutic resistance.
  • DOI:
    10.1016/j.ydbio.2020.12.018
  • 发表时间:
    2021-07
  • 期刊:
  • 影响因子:
    2.7
  • 作者:
    Szulzewsky F;Holland EC;Vasioukhin V
  • 通讯作者:
    Vasioukhin V
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

VALERI VASIOUKHIN其他文献

VALERI VASIOUKHIN的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('VALERI VASIOUKHIN', 18)}}的其他基金

Basal Cell Polarity Proteins in Normal Tissue Homeostasis and Cancer
正常组织稳态和癌症中的基底细胞极性蛋白
  • 批准号:
    10406262
  • 财政年份:
    2019
  • 资助金额:
    $ 39.45万
  • 项目类别:
Basal Cell Polarity Proteins in Normal Tissue Homeostasis and Cancer
正常组织稳态和癌症中的基底细胞极性蛋白
  • 批准号:
    9814413
  • 财政年份:
    2019
  • 资助金额:
    $ 39.45万
  • 项目类别:
Basal Cell Polarity Proteins in Normal Tissue Homeostasis and Cancer
正常组织稳态和癌症中的基底细胞极性蛋白
  • 批准号:
    10601295
  • 财政年份:
    2019
  • 资助金额:
    $ 39.45万
  • 项目类别:
Basal Cell Polarity Proteins in Normal Tissue Homeostasis and Cancer
正常组织稳态和癌症中的基底细胞极性蛋白
  • 批准号:
    10158454
  • 财政年份:
    2019
  • 资助金额:
    $ 39.45万
  • 项目类别:
Alpha-Catenin in Regulation of Tissue Homeostasis and Cancer
α-连环蛋白调节组织稳态和癌症
  • 批准号:
    8643463
  • 财政年份:
    2014
  • 资助金额:
    $ 39.45万
  • 项目类别:
Alpha-Catenin in Regulation of Tissue Homeostasis and Cancer
α-连环蛋白调节组织稳态和癌症
  • 批准号:
    9057992
  • 财政年份:
    2014
  • 资助金额:
    $ 39.45万
  • 项目类别:
Regulation of Hippo Signaling by Src-Family Kinases
Src 家族激酶对 Hippo 信号传导的调节
  • 批准号:
    8764489
  • 财政年份:
    2014
  • 资助金额:
    $ 39.45万
  • 项目类别:
The Hippo Pathway in Prostate Gland Homeostasis and Prostate Cancer
前列腺稳态和前列腺癌中的 Hippo 通路
  • 批准号:
    9228337
  • 财政年份:
    2013
  • 资助金额:
    $ 39.45万
  • 项目类别:
The Hippo Pathway in Prostate Gland Homeostasis and Prostate Cancer
前列腺稳态和前列腺癌中的 Hippo 通路
  • 批准号:
    8517420
  • 财政年份:
    2013
  • 资助金额:
    $ 39.45万
  • 项目类别:
The Hippo Pathway in Prostate Gland Homeostasis and Prostate Cancer
前列腺稳态和前列腺癌中的 Hippo 通路
  • 批准号:
    9005838
  • 财政年份:
    2013
  • 资助金额:
    $ 39.45万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39.45万
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 39.45万
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 39.45万
  • 项目类别:
    Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 39.45万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 39.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 39.45万
  • 项目类别:
    Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
  • 批准号:
    10065645
  • 财政年份:
    2023
  • 资助金额:
    $ 39.45万
  • 项目类别:
    Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 39.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 39.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 39.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了