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CrkI and CrkII Function as Key Signaling Integrators for Migration and Invasion of Cancer Cells
Ist Teil von
Molecular cancer research, 2005-04, Vol.3 (4), p.183-194
Ort / Verlag
United States: American Association for Cancer Research
Erscheinungsjahr
2005
Quelle
MEDLINE
Beschreibungen/Notizen
Crk adaptor proteins play an important role during cellular signaling by mediating the formation of protein complexes. Increased
levels of Crk proteins are observed in several human cancers and overexpression of Crk in epithelial cell cultures promotes
enhanced cell dispersal and invasion, implicating Crk as a regulator of invasive responses. To determine the requirement of
Crk for invasive signals, we targeted the CRKI/II gene by RNA interference. Consistent knockdown of CrkI/II was observed with two small interfering RNA targeting sequences
in all human cancer cell lines tested. CrkI/II knockdown resulted in a significant decrease in migration and invasion of multiple
malignant breast and other human cancer cell lines (MDA-231, MDA-435s, H1299, KB, and HeLa). Moreover, CrkI/II knockdown decreased
cell spreading on extracellular matrix and led to a decrease in actin stress fibers and the formation of mature focal adhesions.
Using immunohistochemistry, we show elevated CrkI/II protein levels in patients with breast adenocarcinoma. Together, these
studies identify Crk adaptor proteins as critical integrators of upstream signals for cell invasion and migration in human
cancer cell lines and support a role for Crk in metastatic spread.