Prostaglandin E2-protein kinase A signaling and protein phosphatases-1 and -2A regulate human head and neck squamous cell carcinoma motility, adherence, and cytoskeletal organization.
Human head and neck squamous cell carcinoma (HNSCC) cultures were established from cancers of two patients. These cells were used to study if phosphorylation reactions by protein kinase A (PKA) and dephosphorylation reactions by protein phosphatases-1 and -2A (PP-1/2A) regulate tumor motility and adhesion to extracellular matrix components, and if this might be associated with cytoskeletal reorganization. Both cultures were motile and adherent to collagen I, fibronectin, vitronectin and laminin. Motility and adhesiveness was dependent on production of prostaglandin E2 PGE2 and on PKA activation. Blocking PP-1/2A activity with okadaic acid resulted in a PKA-dependent increase in m otility and, in some instances, adhesiveness by the HNSCC cells. The okadaic acid-induced increase in motility and adhesiveness coincided with a reduction in filamentous actin. These data suggest PKA and PP-1/2A have opposing effects in regulating the motility, adherence, and actin polymerization.
Research Service (151-Z2), Hines Veterans Affairs Hospital, IL 60141, USA.
Y
Y
Lozano
A
A
Taitz
G J
GJ
Petruzzelli
A
A
Djordjevic
M R
MR
Young
D000199:Actins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism*; D015536:Down-Regulation; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism; D008856:Microscopy, Fluorescence; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000378:metabolism
D000199:Actins; D005353:Fibronectins; D007797:Laminin; D019096:Vitronectin; D019319:Okadaic Acid; D003094:Collagen; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D015232:Dinoprostone; D007213:Indomethacin