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p21-activated kinase signaling in breast cancer.

Gururaj AE, Rayala SK, Kumar R - Breast Cancer Res. (2004)

Bottom Line: The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis.A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer.Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. aegururaj@mdanderson.org

ABSTRACT
The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis. A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue culture studies, and human materials.

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A schematic model of p21-activated kinase (PAK) action in the absence of estrogen in breast cancer cells. A simplified summary of the cellular events in which regulation of cancer-related events by PAKs has been implicated. Both the N-termini and C-termini of PAK can interact with various signaling components and thus promote specific changes required for cells to acquire a cancerous and metastatic phenotype. Broken lines, proposed regulation. ER, estrogen receptor; PKA, protein kinase A.
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Figure 3: A schematic model of p21-activated kinase (PAK) action in the absence of estrogen in breast cancer cells. A simplified summary of the cellular events in which regulation of cancer-related events by PAKs has been implicated. Both the N-termini and C-termini of PAK can interact with various signaling components and thus promote specific changes required for cells to acquire a cancerous and metastatic phenotype. Broken lines, proposed regulation. ER, estrogen receptor; PKA, protein kinase A.

Mentions: Human breast cancers and the cell models derived from them can be classified into those that are steroid hormone dependent and those that grow independent of estradiol. An effect of Pak1, which is important for hormone-dependent breast cancer, is its ability to phosphorylate the ER either directly or indirectly. Wang and colleagues demonstrated that Pak1 phosphorylates the ER at Ser305 and promotes its transactivation (Fig. 3) [25]. Furthermore, transgenic mice that express kinase-active Pak1 develop hyperplasia in the mammary epithelium and have increased expression of ER target genes [23]. In highly metastatic ER-positive breast carcinomas, the locus to which PAK has been mapped, 11q13, is amplified [54]. Steroid hormone-independent subtypes often utilize pathways involving peptide hormones or growth factor. Since Pak1 could be activated by growth factor signaling, these findings imply that Pak1 might regulate the ER pathway in ligand-independent phenotypes.


p21-activated kinase signaling in breast cancer.

Gururaj AE, Rayala SK, Kumar R - Breast Cancer Res. (2004)

A schematic model of p21-activated kinase (PAK) action in the absence of estrogen in breast cancer cells. A simplified summary of the cellular events in which regulation of cancer-related events by PAKs has been implicated. Both the N-termini and C-termini of PAK can interact with various signaling components and thus promote specific changes required for cells to acquire a cancerous and metastatic phenotype. Broken lines, proposed regulation. ER, estrogen receptor; PKA, protein kinase A.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064107&req=5

Figure 3: A schematic model of p21-activated kinase (PAK) action in the absence of estrogen in breast cancer cells. A simplified summary of the cellular events in which regulation of cancer-related events by PAKs has been implicated. Both the N-termini and C-termini of PAK can interact with various signaling components and thus promote specific changes required for cells to acquire a cancerous and metastatic phenotype. Broken lines, proposed regulation. ER, estrogen receptor; PKA, protein kinase A.
Mentions: Human breast cancers and the cell models derived from them can be classified into those that are steroid hormone dependent and those that grow independent of estradiol. An effect of Pak1, which is important for hormone-dependent breast cancer, is its ability to phosphorylate the ER either directly or indirectly. Wang and colleagues demonstrated that Pak1 phosphorylates the ER at Ser305 and promotes its transactivation (Fig. 3) [25]. Furthermore, transgenic mice that express kinase-active Pak1 develop hyperplasia in the mammary epithelium and have increased expression of ER target genes [23]. In highly metastatic ER-positive breast carcinomas, the locus to which PAK has been mapped, 11q13, is amplified [54]. Steroid hormone-independent subtypes often utilize pathways involving peptide hormones or growth factor. Since Pak1 could be activated by growth factor signaling, these findings imply that Pak1 might regulate the ER pathway in ligand-independent phenotypes.

Bottom Line: The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis.A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer.Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. aegururaj@mdanderson.org

ABSTRACT
The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis. A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue culture studies, and human materials.

Show MeSH
Related in: MedlinePlus