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, 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.

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The lncRNA DLX6-AS1 promoted cell proliferation, invasion, migration and epithelial-to-mesenchymal transition in bladder cancer via modulating Wnt/β-catenin signaling pathway

Cancer Cell International ◽

10.1186/s12935-019-1010-z ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 4

Author(s):

Jinan Guo ◽

Zhixin Chen ◽

Hongtao Jiang ◽

Zhou Yu ◽

Junming Peng ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cancer Progression ◽

Bladder Cancer Cell ◽

Mesenchymal Transition ◽

Bladder Cancer Cells

Abstract Background Bladder cancer is the most common human urological malignancies with poor prognosis, and the pathophysiology of bladder cancer involves multi-linkages of regulatory networks in the bladder cancer cells. Recently, the long noncoding RNAs (lncRNAs) have been extensively studied for their role on bladder cancer progression. In this study, we evaluated the expression of DLX6 Antisense RNA 1 (DLX6-AS1) in the cancerous bladder tissues and studied the possible mechanisms of DLX6-AS1 in regulating bladder cancer progression. Methods Gene expression was determined by qRT-PCR; protein expression levels were evaluated by western blot assay; in vitro functional assays were used to determine cell proliferation, invasion and migration; nude mice were used to establish the tumor xenograft model. Results Our results showed the up-regulation of DLX6-AS1 in cancerous bladder cancer tissues and bladder cell lines, and high expression of DLX6-AS1 was correlated with advance TNM stage, lymphatic node metastasis and distant metastasis. The in vitro experimental data showed that DLX6-AS1 overexpression promoted bladder cancer cell growth, proliferation, invasion, migration and epithelial-to-mesenchymal transition (EMT); while DLX6-AS1 inhibition exerted tumor suppressive actions on bladder cancer cells. Further results showed that DLX6-AS1 overexpression increased the activity of Wnt/β-catenin signaling, and the oncogenic role of DLX6-AS1 in bladder cancer cells was abolished by the presence of XAV939. On the other hand, DLX6-AS1 knockdown suppressed the activity of Wnt/β-catenin signaling, and the tumor-suppressive effects of DLX6-AS1 knockdown partially attenuated by lithium chloride and SB-216763 pretreatment. The in vivo tumor growth study showed that DLX6-AS1 knockdown suppressed tumor growth of T24 cells and suppressed EMT and Wnt/β-catenin signaling in the tumor tissues. Conclusion Collectively, the present study for the first time identified the up-regulation of DLX6-AS1 in clinical bladder cancer tissues and in bladder cancer cell lines. The results from in vitro and in vivo assays implied that DLX6-AS1 exerted enhanced effects on bladder cancer cell proliferation, invasion and migration partly via modulating EMT and the activity of Wnt/β-catenin signaling pathway.

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NF-κB suppresses apoptosis and promotes bladder cancer cell proliferation by upregulating survivin expression in vitro and in vivo

Scientific Reports ◽

10.1038/srep40723 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 32

Author(s):

Xiaolu Cui ◽

Dezhi Shen ◽

Chuize Kong ◽

Zhe Zhang ◽

Yu Zeng ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Cell ◽

Survivin Expression ◽

Bladder Cancer Cell ◽

Cancer Cell Proliferation

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MP17-10 N6-METHYLADENOSINE MODIFICATION OF CIRCANKS1A ACCELERATES CYTOPLASMIC EXPORT AND STABILIZES RACGAP1 TO PROMOTE BLADDER CANCER CELL PROLIFERATION AND METASTASIS

The Journal of Urology ◽

10.1097/ju.0000000000000842.010 ◽

2020 ◽

Vol 203 ◽

pp. e229-e230

Author(s):

Qiangqiang Ge* ◽

Yang Xun ◽

Junlin Lu ◽

Shaogang Wang

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Cell ◽

Bladder Cancer Cell ◽

Cancer Cell Proliferation ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis

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Effects of agents that inhibit cellular iron incorporation on bladder cancer cell proliferation

Blood ◽

10.1182/blood.v82.5.1608.1608 ◽

1993 ◽

Vol 82 (5) ◽

pp. 1608-1617 ◽

Cited By ~ 31

Author(s):

PA Seligman ◽

RB Schleicher ◽

G Siriwardana ◽

J Domenico ◽

EW Gelfand

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Cell ◽

Cellular Proliferation ◽

Bladder Cancer Cell ◽

Cancer Cell Proliferation ◽

Inhibition Of Proliferation ◽

Cellular Iron

Abstract Agents that interfere with cellular iron (Fe) incorporation inhibit tumor cell proliferation, including metals that bind to transferrin (Tf) such as gallium (Ga) or indium (In) and Fe chelators such as desferrioxamine (DFO). Ga nitrate is effective in the treatment of metastatic bladder cancer and these patients exhibit evidence for interference with Fe metabolism. We show here that bladder cancer cell proliferation in vitro is dependent on Tf-Fe. Concentrations of DFO that can be readily achieved in vivo inhibit cellular proliferation even in the presence of physiologic concentrations of Tf-Fe. Inhibition of proliferation by Tf-Ga is associated with decreased cellular Fe incorporation. However, when a physiologic concentration of Tf-Fe is added to an equimolar concentration of Tf-Ga, significant Fe incorporation is evident despite inhibition of proliferation. Thus, besides interference with Fe incorporation, Ga may also interfere with intracellular Fe distribution and/or directly inhibit an Fe- (or non-Fe- ) requiring process necessary for cellular proliferation. DFO followed sequentially by Tf-Ga results in marked potentiation of inhibition of proliferation. The effects of this combination appear to be related to both interference with Fe metabolism and increased Ga uptake. This sequential combination may be useful in the treatment of bladder cancer.

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Effects of agents that inhibit cellular iron incorporation on bladder cancer cell proliferation

Blood ◽

10.1182/blood.v82.5.1608.bloodjournal8251608 ◽

1993 ◽

Vol 82 (5) ◽

pp. 1608-1617 ◽

Cited By ~ 1

Author(s):

PA Seligman ◽

RB Schleicher ◽

G Siriwardana ◽

J Domenico ◽

EW Gelfand

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Cell ◽

Cellular Proliferation ◽

Bladder Cancer Cell ◽

Cancer Cell Proliferation ◽

Inhibition Of Proliferation ◽

Cellular Iron

Agents that interfere with cellular iron (Fe) incorporation inhibit tumor cell proliferation, including metals that bind to transferrin (Tf) such as gallium (Ga) or indium (In) and Fe chelators such as desferrioxamine (DFO). Ga nitrate is effective in the treatment of metastatic bladder cancer and these patients exhibit evidence for interference with Fe metabolism. We show here that bladder cancer cell proliferation in vitro is dependent on Tf-Fe. Concentrations of DFO that can be readily achieved in vivo inhibit cellular proliferation even in the presence of physiologic concentrations of Tf-Fe. Inhibition of proliferation by Tf-Ga is associated with decreased cellular Fe incorporation. However, when a physiologic concentration of Tf-Fe is added to an equimolar concentration of Tf-Ga, significant Fe incorporation is evident despite inhibition of proliferation. Thus, besides interference with Fe incorporation, Ga may also interfere with intracellular Fe distribution and/or directly inhibit an Fe- (or non-Fe- ) requiring process necessary for cellular proliferation. DFO followed sequentially by Tf-Ga results in marked potentiation of inhibition of proliferation. The effects of this combination appear to be related to both interference with Fe metabolism and increased Ga uptake. This sequential combination may be useful in the treatment of bladder cancer.

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Tip60 Suppresses Cholangiocarcinoma Proliferation and Metastasis via PI3k-AKT

Cellular Physiology and Biochemistry ◽

10.1159/000494183 ◽

2018 ◽

Vol 50 (2) ◽

pp. 612-628 ◽

Cited By ~ 4

Author(s):

Yaodong Zhang ◽

Guwei Ji ◽

Sheng Han ◽

Zicheng Shao ◽

Zefa Lu ◽

...

Keyword(s):

Cell Proliferation ◽

Cancer Progression ◽

Venous Invasion ◽

In Vivo Studies ◽

Akt Pathway ◽

Rank Test ◽

Aberrant Expression ◽

Proliferation And Metastasis

Background/Aims: Aberrant expression of Tip60 is associated with progression in many cancers. However, the role of Tip60 in cancer progression remains contradictory. The aim of this study was to investigate the clinical significance, biological functions and underlying mechanisms of Tip60 deregulation in cholangiocarcinoma (CCA) for the first time. Methods: Quantitative real-time PCR (QRT-PCR), western blotting and immunohistochemistry staining (IHC) were carried out to measure Tip60 expression in CCA tissues and cell lines. Kaplan–Meier analysis and the log-rank test were used for survival analysis. In vitro, cell proliferation was evaluated by flow cytometry and CCK-8, colony formation, and EDU assays. Migration/ invasion was evaluated by trans-well assays. Phosphokinase array was used to confirm the dominant signal regulated by Tip60. Tumor growth and metastasis were demonstrated in vivo using a mouse model. Results: Tip60 was notably downregulated in CCA tissues, which was associated with greater tumor size, venous invasion, and TNM stage. Down-regulation of Tip60 was associated with tumor progression and poorer survival in CCA patients. In vitro and in vivo studies demonstrated that Tip60 suppressed growth and metastasis throughout the progression of CCA. We further identified the PI3K/AKT pathway as a dominant signal of Tip60 and suggested that Tip60 regulated CCA cell proliferation and metastasis via PT3K-AKT pathway. Pearson analysis revealed that PTEN was positively correlated with the Tip60 level in CCA tissues. Conclusion: Tip60, as a tumor suppressor in CCA via the PI3K/AKT pathway, might be a promising therapeutic target or prognostic marker for CCA.

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