title: Screening of a PKC zeta-specific kinase inhibitor PKCzI257.3 which inhibits EGF-induced breast cancer cell chemotaxis.
abstract: Chemotaxis has recently been implicated in tumor metastasis. Protein Kinase C(PKC)zeta is often over-activated and is a key signal transducer shared by both EGFR- and CXCR4-mediated chemotactic signaling in human breast and lung cancers, as well as CSF-1-induced macrophage migration. In order to develop potential inhibitors targeting PKCzeta for effective blockage of cancer cell chemotaxis and tumor metastasis, the Z'-lyte kinase assay -SER/THR 7 peptide kit was used and a compound called PKCzI257.3 was identified with IC50 of 28 microM. As a result of treatment, chemotactic migration potency of the human breast cancer cell MDA-MB-231 were impaired, while no significant effect was observed on cell proliferation. Furthermore, EGF-induced cofilin phosphorylation, a critical step of cofilin recycle and actin polymerization, was also dampened, which was relevant to the decreased cell migration. Our results suggest that PKCzI257.3 is a PKCzeta-specific compound inhibitor which blocked cancer cell migration and may serve as a potential therapeutic drug for cancer treatment.
authors.affiliation: Key Laboratory of Breast Cancer Prevention and Therapy of the Ministry of Education, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Baogang
authors.initials: B
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Ruifang
authors.initials: R
authors.lastname: Niu
authors.forename: Guoguang
authors.initials: G
authors.lastname: Ying
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang