title: Loss of P53 facilitates invasion and metastasis of prostate cancer cells.
abstract: Prostate cancer is a lethal cancer for the invasion and metastasis in its earlier period. P53 is a tumor suppressor gene which plays a critical role on safeguarding the integrity of genome. However, loss of P53 facilitates or inhibits the invasion and metastasis of tumor is still suspended. In this study, we are going to explain whether loss of P53 affect the invasion and metastasis of prostate cancer cells. To explore whether loss of P53 influences the invasion and metastasis ability of prostate cancer cells, we first compared the invasion ability of si-P53 treated cells and control cells by wound healing, transwell assay, and adhesion assay. We next tested the activity of MMP-2, MMP-9, and MMP-14 by western blot and gelatin zymography. Moreover, we employed WB and IF to identify the EMT containing E-cad, N-cad, vimentin, etc. We also examined the expression of cortactin, cytoskeleton, and paxillin by immunofluorescence, and tested the expression of ERK and JNK by WB. Finally, we applied WB to detect the expression of FAK, Src, and the phosphorylation of them to elucidate the mechanism of si-P53 influencing invasion and metastasis. According to the inhibition rate of si-P53, we choose the optimized volume of si-P53. With the volume, we compare the invasion and metastasis ability of Du145 and si-P53 treated cells. We find si-P53 promotes the invasion and metastasis in prostate cancer cells, increases the expression and activity of MMP-2/9 and MMP-14. Also, si-P53 promotes EMT and cytoskeleton rearrangement. Further analyses explain that this effect is associated with FAK-Src signaling pathway. Loss of P53 promotes the invasion and metastasis ability of prostate cancer cells and the mechanism is correlated with FAK-Src signaling pathway. P53 is involved in the context of invasion and metastasis.
authors: Urology Department, The First Affiliated Hospital of China Medical University, No. 92 Bei'er Road, Heping District, Shenyang, Liaoning, People's Republic of China, lhd373@sohu.com.
authors: Yi
authors: Y
authors: Wang
authors: Y X
authors: YX
authors: Zhang
authors: C Z
authors: CZ
authors: Kong
authors: Z
authors: Z
authors: Zhang
authors: Y Y
authors: YY
authors: Zhu
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D051356:Cortactin / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051356:Cortactin; D051419:Paxillin; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
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