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Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway
| Content Provider | SAGE Publishing |
|---|---|
| Author | Lu, Jian-jun Su, Yao-wu Wang, Chao-jun Li, Di-feng Zhou, Liang |
| Copyright Year | 2019 |
| Abstract | The present study aimed to investigate the role of semaphorin 4D (Sema4D) in bladder cancer cell proliferation and metastasis in vivo and in vitro. Effects of Sema4D modulation on cancer cell viability and clonogenic abilities were assessed by MTT assay and colony formation assay. Cell apoptosis, cell cycle analysis, transwell assays, and wound-healing assays were also assayed. A mouse model of bladder cancer was established to observe the tumorigenesis in vivo. Our data showed that Sema4D was 4-fold upregulated in clinical bladder cancer tissues relative to noncancerous ones and differentially expressed in bladder cancer cell lines. Knockdown of Sema4D in bladder cancer T24 and 5637 cells significantly decreased cell proliferation, clonogenic potential, and motility. On the contrary, overexpression of Sema4D in bladder cancer SV-HUC-1 cells significantly increased cell viability and motility. Concordantly, knockdown of Sema4D impaired while overexpression of Sema4D promoted bladder cancer cell growth rates in xenotransplanted mice. Cell cycle was arrested by modulation of Sema4D. Cell apoptotic rates and the mitochondrial membrane potentials were consistently increased upon knockdown of Sema4D in T24 cells and 5637 cells. Western blotting revealed that epithelial–mesenchymal transition was promoted by Sema4D. The PI3K/AKT pathway was activated upon Sema4D overexpression in SV-HUC-1 cells, while it was inactivated by knockdown of Sema4D in T24 cells. All these data suggest that Sema4D promotes cell proliferation and metastasis in bladder cancer in vivo and in vitro. The oncogenic behavior of Sema4D is achieved by activating the PI3K/AKT pathway. |
| Related Links | https://journals.sagepub.com/doi/pdf/10.1177/0300891618811280?download=true |
| Starting Page | 231 |
| Ending Page | 242 |
| Page Count | 12 |
| ISSN | 03008916 |
| Issue Number | 3 |
| Volume Number | 105 |
| Journal | Tumori Journal (TMJ) |
| e-ISSN | 20382529 |
| DOI | 10.1177/0300891618811280 |
| Language | English |
| Publisher | Sage Publications UK |
| Publisher Date | 2019-01-24 |
| Publisher Place | London |
| Access Restriction | Open |
| Rights Holder | © The Author(s) 2019 |
| Subject Keyword | PI3K/AKT signaling Semaphorin 4D bladder cancer proliferation metastasis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
