Cdc25A protein phosphatase: a therapeutic target for liver cancer therapies.
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.
Wang
Z
Z
Kimmel Cancer Center, Thomas Jefferson University, 233 S 10 Street, Room 519A, Philadelphia, PA, USA.
Kar
S
S
Carr
B I
BI
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D020687:cdc25 Phosphatases