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Pyk2 and Src mediate signaling to CCL18-induced breast cancer metastasis
Hai-Yan Li1, Xiu-Ying Cui, Wei Wu
1Breast 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.
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.
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