Molecular Mechanism of KAI1/CD82-mediated Suppression
Molecular Mechanism of KAI1/CD82-mediated Suppression
批准号:
6781299
负责人:
XIN A ZHANG
金额:
$22.01万
依托单位国家:
美国
项目类别:
财政年份:
2004
资助国家:
美国
项目状态:
已结题
起止时间:
2004-03-01 至 2009-02-28
关键词:
biological signal transductioncell adhesioncell migrationfatty acylationintracellular transportmembrane proteinsmetastasismolecular oncologyneoplasm /cancer invasivenesspalmitatesprostate neoplasmsprotein structure functionsite directed mutagenesistetraspanintissue /cell culturetransfectiontumor suppressor proteins
中文摘要
KAI1/CD82是tetraspanin超家族的成员,作为一种癌症被重新发现
英文摘要
KAI1/CD82 is a member of the tetraspanin superfamily and has been re-discovered as a cancer
metastasis suppressor. But the mechanism of the KAI1/CD82-mediated suppression of cancer metastasis still remains unclear. Similar to other tetraspanins, KAI1/CD82 has been reported to regulate cell migration and cancer cell invasiveness. Our studies indicate that: 1) restoration of the KAI1/CD82 expression in prostate cancer cells inhibits cell motility, 2) the FAK-p130CAS/CrK-paxillin signaling pathway is required for KAI1/CD82-mediated suppression of prostate cancer cell motility, 3) KAI1/CD82 disrupts the formation of motility-related subcellular structures such as focal adhesion and cortical actin network, 4) KASP (or EWI2/PGRL), a novel Ig superfamily protein, was identified as a KAI1/CD82-binding protein, and 5) KASP (or EWI2/PGRL) functionally coordinates with KAI 1/CD82 in cell migration. Therefore, we hypothesize that the KAI1/CD82-mediated suppression of cancer metastasis depends on its inhibition of cell motility through 1) regulating the intracellular signaling pathways that control cell movement, and 2) participating the transmembrane complex that is involved in cell movement. So, we propose to first define the structural and functional elements in KAI1/CD82 molecule responsible for the inhibition of cell motility and invasiveness. In particular, the roles of specific biochemical features such as acylation, internalization, and KASP (or EWl2/PGRL) association in cancer cell motility and invasiveness will be determined, in order to conclusively link a specific biochemical feature of KAI1/CD82 to its inhibition of cell motility. Second, we will assess the
role of KASP (or EWI2/PGRL) in KAI1/CD82-mediated suppression of cancer cell motility and invasiveness. Third, we will assess how the biochemical feature(s) required for the motility-inhibition affects cell motility by analyzing cell motility-related cellular functions such as adhesion, spreading, and vesicle trafficking and cell motility-related molecular signaling. Together, these studies will identify the mechanism responsible for the KAI1/CD82-mediated suppression of cancer metastasis. Understanding the mechanistic roles of KAI1/CD82 in cancer cell motility will promises to lead to the development of therapeutics capable of specially inhibiting
cancer metastasis.
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专著(0)
科研奖励(0)
会议论文
How Tetraspanins Regulate Sepsis
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批准号:10052714
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项目类别:
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资助金额:$29.0万
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财政年份:2020
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负责人:XIN A ZHANG
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依托单位:
How Tetraspanins Regulate Sepsis
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批准号:10654676
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How Tetraspanins Regulate Sepsis
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批准号:10437734
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财政年份:2020
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How Tetraspanins Regulate Sepsis
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资助金额:$29.0万
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依托单位:
Diversity Supplement of R01 grant "How Tetraspanins Regulate Vascular Morphogenesis"
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How Tetraspanins Regulate Vascular Morphogenesis
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资助金额:$42.42万
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How Tetraspanins Regulate Vascular Morphogenesis
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批准号:9362663
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资助金额:$37.0万
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依托单位:
Tetraspanin-enriched microdomains and endothelial barrier function
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资助金额:$37.44万
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财政年份:2016
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负责人:XIN A ZHANG
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依托单位:
Molecular Mechanism of KAI1/CD82-mediated Suppression
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批准号:7178435
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项目类别:
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资助金额:$21.8万
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财政年份:2004
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依托单位:
Molecular Mechanism of KAI1/CD82-mediated Suppression
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批准号:7937533
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项目类别:
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资助金额:$4.64万
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财政年份:2004
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负责人:XIN A ZHANG
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依托单位:
How KAI1/CD82 Suppresses Cancer Invasion and Metastasis
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批准号:8707272
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项目类别:
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资助金额:$4.93万
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财政年份:2004
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负责人:XIN A ZHANG
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依托单位:
How KAI1/CD82 Suppresses Cancer Invasion and Metastasis
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批准号:8213635
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项目类别:
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资助金额:$27.98万
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How KAI1/CD82 Suppresses Cancer Invasion and Metastasis
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资助金额:$22.51万
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依托单位:
Molecular Mmechanism of KAI1/CD82-mediated Suppression
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批准号:7434152
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How KAI1/CD82 Suppresses Cancer Invasion and Metastasis
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How KAI1/CD82 Suppresses Cancer Invasion and Metastasis
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批准号:8792665
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资助金额:$3.92万
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How KAI1/CD82 Suppresses Cancer Invasion and Metastasis
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批准号:8396603
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项目类别:
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资助金额:$8.29万
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How KAI1/CD82 Suppresses Cancer Invasion and Metastasis
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批准号:7891112
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项目类别:
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资助金额:$23.21万
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负责人:XIN A ZHANG
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How KAI1/CD82 Suppresses Cancer Invasion and Metastasis
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资助金额:$4.59万
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财政年份:2004
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负责人:XIN A ZHANG
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依托单位:
国内基金
海外基金
GMFG/F-actin/cell adhesion 轴驱动 EHT 在造
血干细胞生成中的作用及机制研究
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批准号:TGY24H080011
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项目类别:省市级项目
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资助金额:--
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批准年份:2024
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负责人:李鸿鹄
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依托单位: