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The Role of Intermediate Filaments i...

Kidd, Martha Ellen.

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The Role of Intermediate Filaments in the Metastatic Spread of Non-Small Cell Lung Cancer.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	The Role of Intermediate Filaments in the Metastatic Spread of Non-Small Cell Lung Cancer./
Author:	Kidd, Martha Ellen.
Description:	99 p.
Notes:	Source: Dissertation Abstracts International, Volume: 75-01(E), Section: B.
Contained By:	Dissertation Abstracts International75-01B(E).
Subject:	Biology, General. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3595629
ISBN:	9781303414794

The Role of Intermediate Filaments in the Metastatic Spread of Non-Small Cell Lung Cancer.
Kidd, Martha Ellen.

The Role of Intermediate Filaments in the Metastatic Spread of Non-Small Cell Lung Cancer. - 99 p.

Source: Dissertation Abstracts International, Volume: 75-01(E), Section: B.

Thesis (Ph.D.)--Northwestern University, 2013.

There is an accumulation of evidence in the literature demonstrating the integral role of vimentin intermediate filaments in the progression of lung cancers. Vimentin intermediate filament proteins have been implicated in many aspects of cancer initiation and progression, including tumorigenesis, EMT, and the metastatic spread of cancer. Furthermore, vimentin intermediate filaments have been implicated in increased cellular migration and invasion rates associated with EMT. While it is commonly accepted as a marker of EMT, recent evidence has pointed to vimentin intermediate filaments having a pivotal role in cellular motility and cancer metastasis. However, the role of vimentin intermediate filaments in the spread of lung cancer is still largely unknown. We provide data showing vimentin expression to be required for increased cellular invasion and migration associated with the hypoxic tumor microenvironment. This increase in migration may be due to changes in vimentin distribution, which affect cellular polarity necessary for efficient migration. Furthermore, we have shown vimentin may mediate increased invasion and migration associated with the hypoxic microenvironment via an AKT dependent pathway. In the hypoxic microenvironment, we have shown AKT 2 to mediate invasion and AKT 1 to mediate migration. Vimentin was shown to interact with activated AKT as well as AKT 1 and AKT 2 as demonstrated by coimmunoprecipitation assays. In an in vivo model of non-small cell lung cancer (NSCLC) we have shown vimentin expression to mediate the metastatic spread of lung cancer. Finally, vimentin upregulation is associated with metastatic NSCLC and in matched lymph node metastasis in patient samples; showing vimentin to be an attractive potential marker for metastasis in NSCLC. These results show vimentin to be required for hypoxic mediated invasion and migration and to be a key regulator of the metastatic spread of NSCLC.

ISBN: 9781303414794Subjects--Topical Terms:

1018625
Biology, General.

The Role of Intermediate Filaments in the Metastatic Spread of Non-Small Cell Lung Cancer.
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100 1 $a Kidd, Martha Ellen. $3 2099957
245 1 4 $a The Role of Intermediate Filaments in the Metastatic Spread of Non-Small Cell Lung Cancer.
300 $a 99 p.
500 $a Source: Dissertation Abstracts International, Volume: 75-01(E), Section: B.
500 $a Advisers: Matthew R. Glucksberg; Karen M. Ridge.
502 $a Thesis (Ph.D.)--Northwestern University, 2013.
520 $a There is an accumulation of evidence in the literature demonstrating the integral role of vimentin intermediate filaments in the progression of lung cancers. Vimentin intermediate filament proteins have been implicated in many aspects of cancer initiation and progression, including tumorigenesis, EMT, and the metastatic spread of cancer. Furthermore, vimentin intermediate filaments have been implicated in increased cellular migration and invasion rates associated with EMT. While it is commonly accepted as a marker of EMT, recent evidence has pointed to vimentin intermediate filaments having a pivotal role in cellular motility and cancer metastasis. However, the role of vimentin intermediate filaments in the spread of lung cancer is still largely unknown. We provide data showing vimentin expression to be required for increased cellular invasion and migration associated with the hypoxic tumor microenvironment. This increase in migration may be due to changes in vimentin distribution, which affect cellular polarity necessary for efficient migration. Furthermore, we have shown vimentin may mediate increased invasion and migration associated with the hypoxic microenvironment via an AKT dependent pathway. In the hypoxic microenvironment, we have shown AKT 2 to mediate invasion and AKT 1 to mediate migration. Vimentin was shown to interact with activated AKT as well as AKT 1 and AKT 2 as demonstrated by coimmunoprecipitation assays. In an in vivo model of non-small cell lung cancer (NSCLC) we have shown vimentin expression to mediate the metastatic spread of lung cancer. Finally, vimentin upregulation is associated with metastatic NSCLC and in matched lymph node metastasis in patient samples; showing vimentin to be an attractive potential marker for metastasis in NSCLC. These results show vimentin to be required for hypoxic mediated invasion and migration and to be a key regulator of the metastatic spread of NSCLC.
590 $a School code: 0163.
650 4 $a Biology, General. $3 1018625
650 4 $a Engineering, Biomedical. $3 1017684
650 4 $a Health Sciences, Oncology. $3 1018566
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710 2 $a Northwestern University. $b Biomedical Engineering. $3 1064569
773 0 $t Dissertation Abstracts International $g 75-01B(E).
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792 $a 2013
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3595629