Upregulation and activation of PKCα by ErbB2 through Src promotes breast cancer cell invasion that can be blocked by combined treatment with PKCα and Src inhibitors

摘要: Although ErbB2 is known to enhance breast cancer metastasis, the signaling events responsible for this remain elusive. Alpha-isozyme of protein kinase C (PKCalpha), which involved in development and progression, has been suggested be activated by without direct evidence. In addition, roles PKCalpha ErbB2-mediated cell malignancy have not clearly identified. study, we investigated whether can activate determined what role plays invasion. We expressed wild-type mutant with altered capacities MDA-MB-435 cells revealed that overexpression or activation upregulated downregulation small-interfering RNA decreased expression activity BT474 cells. These vitro results were supported data from patient samples. 150 tumor samples, ErbB2-overexpressing tumors showed significantly higher positive rates membrane immunohistochemistry staining than ErbB2-low-expressing tumors. Mechanistically, found co-immunoprecipitated Src inhibitor PP2 a dominant-negative Src. Moreover, upregulation urokinase-type plasminogen activator receptor (uPAR) reduced either Go6976 PP2, combination superior agent alone suppressing uPAR demonstrate critical invasion provide valuable insights current future clinical trials.