Cargando…

Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway

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, ce...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Jian-jun, Su, Yao-wu, Wang, Chao-jun, Li, Di-feng, Zhou, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566455/
https://www.ncbi.nlm.nih.gov/pubmed/30674231
http://dx.doi.org/10.1177/0300891618811280
_version_ 1783426856021655552
author Lu, Jian-jun
Su, Yao-wu
Wang, Chao-jun
Li, Di-feng
Zhou, Liang
author_facet Lu, Jian-jun
Su, Yao-wu
Wang, Chao-jun
Li, Di-feng
Zhou, Liang
author_sort Lu, Jian-jun
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6566455
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-65664552019-07-22 Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway Lu, Jian-jun Su, Yao-wu Wang, Chao-jun Li, Di-feng Zhou, Liang Tumori Original Research Articles 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. SAGE Publications 2019-01-24 2019-06 /pmc/articles/PMC6566455/ /pubmed/30674231 http://dx.doi.org/10.1177/0300891618811280 Text en © The Author(s) 2019 http://www.creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research Articles
Lu, Jian-jun
Su, Yao-wu
Wang, Chao-jun
Li, Di-feng
Zhou, Liang
Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway
title Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway
title_full Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway
title_fullStr Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway
title_full_unstemmed Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway
title_short Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway
title_sort semaphorin 4d promotes the proliferation and metastasis of bladder cancer by activating the pi3k/akt pathway
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566455/
https://www.ncbi.nlm.nih.gov/pubmed/30674231
http://dx.doi.org/10.1177/0300891618811280
work_keys_str_mv AT lujianjun semaphorin4dpromotestheproliferationandmetastasisofbladdercancerbyactivatingthepi3kaktpathway
AT suyaowu semaphorin4dpromotestheproliferationandmetastasisofbladdercancerbyactivatingthepi3kaktpathway
AT wangchaojun semaphorin4dpromotestheproliferationandmetastasisofbladdercancerbyactivatingthepi3kaktpathway
AT lidifeng semaphorin4dpromotestheproliferationandmetastasisofbladdercancerbyactivatingthepi3kaktpathway
AT zhouliang semaphorin4dpromotestheproliferationandmetastasisofbladdercancerbyactivatingthepi3kaktpathway