title: PBX3 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition.
abstract: The overexpression of pre-leukemia transcription factor 3 (PBX3) in tumors plays an important role in invasion, metastasis and proliferation in a variety of human cancer types. Tumor metastasis and angiogenesis significantly contribute to the progression of cancer and create challenges for cancer therapy. In the present study, reverse transcription-polymerase chain reaction demonstrated that PBX3 was upregulated in gastric cancer (GC) tissues and Transwell assay revealed that the overexpression of PBX3 promoted GC invasion and metastasisin vitro. In addition, a nude mouse xenograft model was established, which demonstrated that PBX3 promoted peritoneal metastasesin vivo. Furthermore, the overexpression of PBX3 in GC promoted the tubular formation of human umbilical vein endothelial cells. Western blot analysis revealed that overexpressed PBX3 induced epithelial-mesenchymal transition (EMT) in GC, as measured by increases in the EMT protein markers N-cadherin and vimentin, while E-cadherin expression was reduced in PBX3-overexpressing GC cells. Contrasting results were observed in PBX3-knockdown GC cells. Additionally, the overexpression of PBX3 increased the levels of phosphorylated AKT (Ser473), which is involved in the progression of a variety of human cancers. Gelatin zymography assay demonstrated that the overexpression of PBX3 also elevated matrix metalloproteinase-9 activity in GC, which was closely associated with tumor metastasis and angiogenesis. Based on these findings, it may be concluded that PBX3 enhances invasion and metastasis in GC by promoting EMT, possibly via the AKT signaling pathway.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Shuanhu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230000, P.R. China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Chungen
authors.initials: C
authors.lastname: Xing
keywords: AKT; PBX3; epithelial-mesenchymal transition; gastric cancer; metastasis