B7-H3 Promotes the Migration and Invasion of Human Bladder Cancer Cells via the PI3K/Akt/STAT3 Signaling Pathway

  • J Cancer. 2017 Feb 25;8(5):816-824. doi: 10.7150/jca.17759.
Yuchao Li  1 Guoning Guo  2 Jie Song  3 Zhiping Cai  3 Jin Yang  4 Zhiwen Chen  5 Yun Wang  4 Yaqin Huang  4 Qiangguo Gao  4
Affiliations
  • 1. Department of Cell Biology, Third Military Medical University, Chongqing 400038, China;; Trainee Brigade, Third Military Medical University, Chongqing 400038, China.
  • 2. Department of Emergency, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
  • 3. Trainee Brigade, Third Military Medical University, Chongqing 400038, China.
  • 4. Department of Cell Biology, Third Military Medical University, Chongqing 400038, China.
  • 5. Urology Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Abstract

Bladder Cancer is one of most common malignant Cancer. Although previous studies have found abnormal expression of B7-H3 in human bladder Cancer tissues, the exact role and molecular mechanism of B7-H3 in bladder Cancer remain unknown. In this study, we first detected the expression of B7-H3 in human bladder Cancer samples and cell lines, and analyzed its correlations with clinicopathological pathological parameters. Next, siRNAs or overexpression plasmids of B7-H3 were transfected into T24 or 5637 cells, and cell proliferation, Apoptosis, migration and invasion were analyzed via CCK-8, colony formation, flow cytometry and transwell assays, protein expression levels were determined by western blotting. The results presented here showed B7-H3 was upregulated in bladder Cancer samples compared with normal tissues, and the expression level was correlated with local invasion status. B7-H3 did not affect cell proliferation and Apoptosis, but cell migration and invasion were changed through the regulation of matrix metalloproteinase (MMP) 2/9. Knockdown of B7-H3 resulted in decreased activity of the STAT3 and PI3K/Akt pathways, and the Akt served as an upstream regulator of the STAT3. Our results suggest that the overexpression of B7-H3 promotes the migration and invasion of human bladder Cancer cells through the PI3K/Akt/STAT3 signaling pathway.

Keywords
B7-H3; MMP; PI3K/Akt/STAT3; human bladder cancer; invasion; migration.
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