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LIMK1 Promotes MT1-MMP Expression and Localization to the Plasma Membrane

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Date Issued:
2012
Abstract/Description:
LIM Kinase 1 (LIMK1), a serine/threonine kinase, modulates actin polymerization and microtubule assembly. The function of LIMK1 is regulated by kinases that are activated by Rho and Rac GTPases. LIMK1 is overexpressed in various cancerous cell types and tissues and its overexpression promotes increased invasion and metastasis of breast and prostate cancer cells. The Membrane-Type Matrix Metalloproteinase 1 (MT1-MMP) is a member of the zinc-binding collagenase family, which is involved in extracellular matrix breakdown and activation of secreted MMP-2. The balance between activation and inhibition of MT1-MMP and MMP-2 helps maintaining normal extracellular matrix turnover. However, it has been shown that elevated MT1-MMP expression can cause excessive ECM digestion and promote tumor invasion and metastasis. Since RhoA and Rac1 have been implicated in metastasis and invasion along with LIMK1 activation, we investigated a possible link between LIMK1 and MT1-MMP. Our results show that the level of MT1-MMP expression is correlated with that of LIMK1 and LIMK1 acts as a transcriptional regulator of MT1-MMP. Additionally, we show that LIMK1 physically associates with MT1-MMP and promotes its translocation to the plasma membrane.
Title: LIMK1 Promotes MT1-MMP Expression and Localization to the Plasma Membrane.
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Name(s): Ottman, Richard, Author
Chakrabarti, Ratna, Committee Chair
Cole, Alexander, Committee Member
Zervos, Antonis, Committee Member
, Committee Member
University of Central Florida, Degree Grantor
Type of Resource: text
Date Issued: 2012
Publisher: University of Central Florida
Language(s): English
Abstract/Description: LIM Kinase 1 (LIMK1), a serine/threonine kinase, modulates actin polymerization and microtubule assembly. The function of LIMK1 is regulated by kinases that are activated by Rho and Rac GTPases. LIMK1 is overexpressed in various cancerous cell types and tissues and its overexpression promotes increased invasion and metastasis of breast and prostate cancer cells. The Membrane-Type Matrix Metalloproteinase 1 (MT1-MMP) is a member of the zinc-binding collagenase family, which is involved in extracellular matrix breakdown and activation of secreted MMP-2. The balance between activation and inhibition of MT1-MMP and MMP-2 helps maintaining normal extracellular matrix turnover. However, it has been shown that elevated MT1-MMP expression can cause excessive ECM digestion and promote tumor invasion and metastasis. Since RhoA and Rac1 have been implicated in metastasis and invasion along with LIMK1 activation, we investigated a possible link between LIMK1 and MT1-MMP. Our results show that the level of MT1-MMP expression is correlated with that of LIMK1 and LIMK1 acts as a transcriptional regulator of MT1-MMP. Additionally, we show that LIMK1 physically associates with MT1-MMP and promotes its translocation to the plasma membrane.
Identifier: CFE0004581 (IID), ucf:49208 (fedora)
Note(s): 2012-12-01
M.S.
Medicine, Molecular Biology and Micro
Masters
This record was generated from author submitted information.
Subject(s): LIM Kinase 1 -- MT1-MMP
Persistent Link to This Record: http://purl.flvc.org/ucf/fd/CFE0004581
Restrictions on Access: public 2012-12-15
Host Institution: UCF

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