Cell Cycle.2019 Oct;18(19):2432-2446.doi: 10.1080/15384101.2019.1648956.Epub 2019 Aug 25.

The involvement of FBP1 in prostate cancer cell epithelial mesenchymal transition, invasion and metastasis by regulating the MAPK signaling pathway

Yan-Ping Zhang  1 Kai-Long Liu  1 Zhan Yang  1 Bao-Sai Lu  1 Jin-Chun Qi  1 Zhen-Wei Han  1 Yue-Wei Yin  1 Ming Zhang  1 De-Min Chen  1 Xiao-Wei Wang  1 Wei Li  1 Hong Xin  2 Affiliations

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Prostate cancer (PCa) is a frequently occurring malignancy in males, and epithelial mesenchymal transition (EMT) plays a critical role in PCa metastasis. Thus, developing biomarkers inhibiting EMT may provide significance for treatment of PCa. Hence, the aim of the current study was to investigate the mechanism by which FBP1 gene silencing influences PCa cell EMT, invasion and metastasis by mediating the MAPK pathway. PCa cell lines exhibiting the highest FBP1 expression were selected and treated with plasmids of siRNA-FBP1 sequence 1 and 2, pcDNA3.1-Flag-FBP1 (over-expression plasmid of FBP1), U0126 (an inhibitor of the ERK signaling pathway) and PD98059 (an inhibitor of the MEK signaling pathway). Cell proliferation, migration and invasion were detected by MTT assay, wound healing assay and Transwell assay, respectively. The mRNA and protein expression of related factors of EMT and MAPK signaling were determined by RT-qPCR and western blot analysis, respectively. Xenograft tumor growth after inoculation of DU145 cells was regularly analyzed in the nude mice. The positive expression of EMT markers was determined by immunohistochemistry. DU-145 and PC-3 cells displaying the highest FBP1 expression were selected for further analysis. The PCa cells treated with siRNA-FBP1 exhibited increased proliferation, migration rate and invasion, in addition to facilitated xenograft tumor growth. Notably, siRNA-FBP1 was identified to accelerate PCa cell EMT by elevating the expression of Vimentin and N-cadherin while diminishing E-cadherin expression via activation of the MAPK signaling pathway. The aforementioned results were reversed in PCa cells treated by pcDNA3.1-Flag-FBP1. Evidence has been provided in this study that FBP1 gene silencing activates the MAPK pathway, which ultimately promotes cell EMT, invasion and metastasis in PCa.

Keywords: FBP1; MAPK signaling pathway; epithelial-mesenchymal transition; invasion; metastasis; prostate cancer.