title: Pyk2 and Src mediate signaling to CCL18-induced breast cancer metastasis.
abstract: Pyk2 and Src phosphorylation is initiated by CCL18, which promotes breast cancer metastasis via its functional G protein-coupled receptor PITPNM3. However, the function of Pyk2 and Src in CCL18-induced breast cancer metastasis is poorly understood. Quantitative reverse-transcription polymerase chain reactions (qRT-PCRs), Western blot, boyden chamber assay, and adherence assay were performed to delineate the consequences of Pyk2/Src in CCL18-induced breast cancer cells. Co-immunoprecipitation and immunofluorescence were performed to analyze the interaction of proteins. Upon the binding of CCL18 to PITPNM3, Pyk2 translocates from the cytoplasm to the plasma membrane to form a stable complex with PITPNM3, subsequently activating Src kinase. Moreover, upon stimulation with CCL18, Pyk2 and Src become essential for integrin alpha5/beta1 clustering-dependent adherence, migration, and invasion. Pyk2 and Src are important in CCL18-induced breast cancer metastasis.
authors.affiliation: Breast Cancer Center, Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, 510120, People's Republic of China; Department of Breast and Thyroid Surgery, The 6th Affriciated Hospital of Sun Yat-Sen University, Sun-Yat-Sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Li
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Cui
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Feng-Yan
authors.initials: FY
authors.lastname: Yu
authors.forename: He-Rui
authors.initials: HR
authors.lastname: Yao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Er-Wei
authors.initials: EW
authors.lastname: Song
authors.forename: Jing-Qi
authors.initials: JQ
authors.lastname: Chen
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D019742:Chemokines, CC / Q000235:genetics*; D005260:Female; D051418:Focal Adhesion Kinase 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009362:Neoplasm Metastasis; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C111792:CCL18 protein, human; D002135:Calcium-Binding Proteins; D019742:Chemokines, CC; D008565:Membrane Proteins; C117885:PITPNM3 protein, human; D051418:Focal Adhesion Kinase 2; D019061:src-Family Kinases
keywords: CCL18; INTEGRIN; METASTASIS; Pyk2; Src