p140Cap protein suppresses tumour cell properties, regulating Csk and Src kinase activity.
We recently identified p140Cap as a novel adaptor protein, expressed in epithelial-rich tissues and phosphorylated upon cell matrix adhesion and growth factor treatment. Here, we characterise p140Cap as a novel Src-binding protein, which regulates Src activation via C-terminal Src kinase (Csk). p140Cap silencing increases cell spreading, migration rate and Src kinase activity. Accordingly, increased expression of p140Cap activates Csk, leading to inhibition of Src and downstream signalling as well as of cell motility and invasion. Moreover, cell proliferation and "in vivo" breast cancer cell growth are strongly impaired by high levels of p140Cap, providing the first evidence that p140Cap is a novel negative regulator of tumour growth.
Di Stefano
Paola
P
Molecular Biotechnology Center, University of Torino, Via Nizza 52, Turin 10126, Italy.
Damiano
Laura
L
Cabodi
Sara
S
Aramu
Simona
S
Tordella
Luca
L
Praduroux
Alice
A
Piva
Roberto
R
Cavallo
Federica
F
Forni
Guido
G
Silengo
Lorenzo
L
Tarone
Guido
G
Turco
Emilia
E
Defilippi
Paola
P
D033942:Adaptor Proteins, Vesicular Transport; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D004789:Enzyme Activation; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D034741:RNA, Small Interfering; C532615:SRCIN1 protein, human; D025521:Tumor Suppressor Proteins; C086603:Matk protein, mouse; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases