The catalytic class I(A) PI3K isoforms play divergent roles in breast cancer cell migration.
Transforming growth factor-β (TGFβ) plays an important role in breast cancer metastasis. Here phosphoinositide 3-kinase (PI3K) signalling was found to play an essential role in the enhanced migration capability of fibroblastoid cells (FibRas) derived from normal mammary epithelial cells (EpH4) by transduction of oncogenic Ras (EpRas) and TGFβ1. While expression of the PI3K isoform p110δ was down-regulated in FibRas cells, there was an increase in the expression of p110α and p110β in the fibroblastoid cells. The PI3K isoform p110β was found to specifically contribute to cell migration in FibRas cells, while p110α contributed to the response in EpH4, EpRas and FibRas cells. Akt, a downstream targets of PI3K signalling, had an inhibitory role in the migration of transformed breast cancer cells, while Rac, Cdc42 and the ribosomal protein S6 kinase (S6K) were necessary for the response. Together our data reveal a novel specific function of the PI3K isoform p110β in the migration of cells transformed by oncogenic H-Ras and TGF-β1.
Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, 8032 Zurich, Switzerland.
Angela
A
De Laurentiis
Olivier E
OE
Pardo
Andrea
A
Palamidessi
Shaun P
SP
Jackson
Simone M
SM
Schoenwaelder
Ernst
E
Reichmann
Giorgio
G
Scita
Alexandre
A
Arcaro
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology*; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000096:biosynthesis / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000201:enzymology; D015536:Down-Regulation; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D011905:Genes, ras; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C083430:Eps8 protein, mouse; D007527:Isoenzymes; D053773:Transforming Growth Factor beta1; D058543:Class Ia Phosphatidylinositol 3-Kinase