Cdc25A Protein Phosphatase: A Therapeutic Target for Liver Cancer Therapies

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
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Cdc25A Protein Phosphatase: A Therapeutic Target for Liver Cancer Therapies



Anti-Cancer Agents in Medicinal Chemistry, 8(8): 863-871.

Author(s): Z. Wang, S. Kar and B I Carr.

Affiliation: Kimmel Cancer Center, Thomas Jefferson University, 233 S 10th Street, Room 519A, Philadelphia, PA, USA.

Abstract

Cdc25A, a dual specificity protein phosphatase, is well-recognized as a critical regulator for cell cycle progression. We recently found that it also regulates mitogen-activated protein kinase (MAPK) signal transduction pathway. Inhibition of Cdc25A activity by a K vitamin analog Compound 5 (Cpd 5) can induce a strong and prolonged activation of epidermal growth factor receptor (EGFR)- MAPK pathway, which leads to suppression of transcription factors CREB and c-Myc, resulting in decreased expression of Cdc25A and cyclin D1 levels. Our investigations suggest that Cdc25A plays a central role in regulating and linking cell cycle progression and MAPK signal transduction pathways. Several other recently synthesized K vitamin analogs also affect this pathway, including the non-quinone PM20 and fluoro-Cpd 5. Thus, searching for new and efficient small molecules to inhibit Cdc25A activity may provide new means to control cancers of the liver and other sites.

Keywords:

Hepatoma, Cdc25A, compound 5, protein phosphatases, cell growth inhibition, MAP kinase, cell cycle, tyrosine phosphorylation.



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Article Details

Volume: 8
Issue Number: 8
First Page: 863
Last Page: 871
Page Count: 9
DOI: 10.2174/187152008786847675
Price: $58
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