Molecular basis for HEF1/NEDD9/Cas-L action as a multifunctional co-ordinator of invasion, apoptosis and cell cycle

Mahendra K. Singh; Lauren Cowell; Sachiko Seo; Geraldine M. O'Neill; Erica A. Golemis

doi:10.1007/s12013-007-0036-3

Molecular basis for HEF1/NEDD9/Cas-L action as a multifunctional co-ordinator of invasion, apoptosis and cell cycle

Mahendra K. Singh, Lauren Cowell, Sachiko Seo, Geraldine M. O'Neill, Erica A. Golemis

Research output: Contribution to journal › Review article › peer-review

88 Scopus citations

Abstract

Upregulation of the scaffolding protein HEF1, also known as NEDD9 and Cas-L, has recently been identified as a pro-metastatic stimulus in a number of different solid tumors, and has also been strongly associated with pathogenesis of BCR-Abl-dependent tumors. As the evidence mounts for HEF1/NEDD9/Cas-L as a key player in metastatic cancer, it is timely to review the molecular regulation of HEF1/NEDD9/Cas-L. Most of the mortality associated with cancer arises from uncontrolled metastases, thus a better understanding of the properties of proteins specifically associated with promotion of this process may yield insights that improve cancer diagnosis and treatment. In this review, we summarize the extensive literature regarding HEF1/NEDD9/Cas-L expression and function in signaling relevant to cell attachment, migration, invasion, cell cycle, apoptosis, and oncogenic signal transduction. The complex function of HEF1/NEDD9/Cas-L revealed by this analysis leads us to propose a model in which alleviation of cell cycle checkpoints and acquired resistance to apoptosis is permissive for a HEF1/NEDD9/Cas-L-promoted pro-metastatic phenotype.

Original language	English (US)
Pages (from-to)	54-72
Number of pages	19
Journal	Cell biochemistry and biophysics
Volume	48
Issue number	1
DOIs	https://doi.org/10.1007/s12013-007-0036-3
State	Published - May 2007
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgments MKS and EAG were supported by NIH RO1 CA63366, a Department of Defense OCRF IDEA Award, Pennsylvania Tobacco Settlement Funds, and a grant from the Susan B. Komen Foundation (to EAG), and by an Appropriation from the Commonwealth of Pennsylvania, and by NIH core Grant CA-06927 (to Fox Chase Cancer Center). SS was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Ministry of Health, Labor, and Welfare of Japan. GMO’N is the NSW Cancer Council Career Development Fellow. LC is supported by an Australian Post-graduate Award and is a NSW Cancer Institute Scholar.

Keywords

Apoptosis
Cas-L
HEF1
HEF1/NEDD9/Cas-L
Invasion
Metastasis
Mitosis
NEDD9
Scaffolding adaptor protein
Signal transduction

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Molecular basis for HEF1/NEDD9/Cas-L action as a multifunctional co-ordinator of invasion, apoptosis and cell cycle",

abstract = "Upregulation of the scaffolding protein HEF1, also known as NEDD9 and Cas-L, has recently been identified as a pro-metastatic stimulus in a number of different solid tumors, and has also been strongly associated with pathogenesis of BCR-Abl-dependent tumors. As the evidence mounts for HEF1/NEDD9/Cas-L as a key player in metastatic cancer, it is timely to review the molecular regulation of HEF1/NEDD9/Cas-L. Most of the mortality associated with cancer arises from uncontrolled metastases, thus a better understanding of the properties of proteins specifically associated with promotion of this process may yield insights that improve cancer diagnosis and treatment. In this review, we summarize the extensive literature regarding HEF1/NEDD9/Cas-L expression and function in signaling relevant to cell attachment, migration, invasion, cell cycle, apoptosis, and oncogenic signal transduction. The complex function of HEF1/NEDD9/Cas-L revealed by this analysis leads us to propose a model in which alleviation of cell cycle checkpoints and acquired resistance to apoptosis is permissive for a HEF1/NEDD9/Cas-L-promoted pro-metastatic phenotype.",

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note = "Funding Information: Acknowledgments MKS and EAG were supported by NIH RO1 CA63366, a Department of Defense OCRF IDEA Award, Pennsylvania Tobacco Settlement Funds, and a grant from the Susan B. Komen Foundation (to EAG), and by an Appropriation from the Commonwealth of Pennsylvania, and by NIH core Grant CA-06927 (to Fox Chase Cancer Center). SS was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Ministry of Health, Labor, and Welfare of Japan. GMO{\textquoteright}N is the NSW Cancer Council Career Development Fellow. LC is supported by an Australian Post-graduate Award and is a NSW Cancer Institute Scholar.",

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N2 - Upregulation of the scaffolding protein HEF1, also known as NEDD9 and Cas-L, has recently been identified as a pro-metastatic stimulus in a number of different solid tumors, and has also been strongly associated with pathogenesis of BCR-Abl-dependent tumors. As the evidence mounts for HEF1/NEDD9/Cas-L as a key player in metastatic cancer, it is timely to review the molecular regulation of HEF1/NEDD9/Cas-L. Most of the mortality associated with cancer arises from uncontrolled metastases, thus a better understanding of the properties of proteins specifically associated with promotion of this process may yield insights that improve cancer diagnosis and treatment. In this review, we summarize the extensive literature regarding HEF1/NEDD9/Cas-L expression and function in signaling relevant to cell attachment, migration, invasion, cell cycle, apoptosis, and oncogenic signal transduction. The complex function of HEF1/NEDD9/Cas-L revealed by this analysis leads us to propose a model in which alleviation of cell cycle checkpoints and acquired resistance to apoptosis is permissive for a HEF1/NEDD9/Cas-L-promoted pro-metastatic phenotype.

AB - Upregulation of the scaffolding protein HEF1, also known as NEDD9 and Cas-L, has recently been identified as a pro-metastatic stimulus in a number of different solid tumors, and has also been strongly associated with pathogenesis of BCR-Abl-dependent tumors. As the evidence mounts for HEF1/NEDD9/Cas-L as a key player in metastatic cancer, it is timely to review the molecular regulation of HEF1/NEDD9/Cas-L. Most of the mortality associated with cancer arises from uncontrolled metastases, thus a better understanding of the properties of proteins specifically associated with promotion of this process may yield insights that improve cancer diagnosis and treatment. In this review, we summarize the extensive literature regarding HEF1/NEDD9/Cas-L expression and function in signaling relevant to cell attachment, migration, invasion, cell cycle, apoptosis, and oncogenic signal transduction. The complex function of HEF1/NEDD9/Cas-L revealed by this analysis leads us to propose a model in which alleviation of cell cycle checkpoints and acquired resistance to apoptosis is permissive for a HEF1/NEDD9/Cas-L-promoted pro-metastatic phenotype.

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Molecular basis for HEF1/NEDD9/Cas-L action as a multifunctional co-ordinator of invasion, apoptosis and cell cycle

Abstract

Bibliographical note

Keywords

UN SDGs

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