The clinicopathological and prognostic value of CD44 expression in bladder cancer: a study based on meta-analysis and TCGA data

Hu, Yu; Zhang, Yongrui; Gao, Jialin; Lian, Xin; Wang, Yuantao

doi:10.1080/21655979.2020.1765500

“…As shown in Supplementary Fig 3 , ITPR3 and CSC markers such as CD44, SOX2 and OCT4 were enriched in BCa stem cells, which indicated that ITPR3 might play a vital role in maintaining the cancer stemness phenotype. We demonstrated that ITPR3 depletion suppressed cancer cell proliferation, migration, invasion and stemness by inhibiting the expression of CD44, which is the main cancer stem cell marker in bladder cancer 40 .…”

Section: Discussionmentioning

confidence: 92%

ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-ĸB/CD44 pathway in urinary bladder carcinoma

Zhang

¹

,

Wang

²

,

Yue

³

et al. 2021

Preprint

0

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Background: Bladder carcinoma is one of the most common urological cancers. ITPR3, as a ubiquitous endoplasmic reticulum calcium channel protein, was reported to be involved in the development and progression of various types of cancer. However, the potential roles and molecular mechanism of ITPR3 in bladder cancer are still unclear. Herein, we elucidated a novel role of ITPR3 in regulating the proliferation, metastasis, and stemness of bladder cancer cells.Methods: The expression of ITPR3 in bladder cancer was analyzed using public databases and bladder cancer tissue microarrays. To demonstrate the role of ITPR3 in regulating the NF-ĸB/CD44 pathway and the progression of bladder cancer, a series of molecular biology and biochemistry methods was performed on clinical tissues, along with in vivo and in vitro experiments. The methods used included western blot assay, quantitative RT-PCR assay, immunofluorescence assay, immunohistochemistry (IHC) assays, wound healing assay, Transwell assay, colony formation assay, tumorsphere formation assay, cell flow cytometry analysis, EdU assay, MTT assay, cell transfection, bisulfite sequencing PCR (BSP), a xenograft tumor model and a tail vein cancer metastasis model.Results: Higher ITPR3 expression was found in bladder cancer tissues and bladder cancer cells compared with the corresponding normal peritumor tissues and SV-HUC-1 cells, which was attributed to demethylation in the ITPR3 promoter region. ITPR3 promoted the proliferation of bladder cancer by accelerating cell cycle transformation and promoted local invasion and distant metastasis by inducing epithelial-to-mesenchymal transition (EMT). Meanwhile, ITPR3 maintained the cancer stemness phenotype by regulating CD44 expression. NF-κB, which is upstream of CD44, also played a critical role in this process.Conclusions: Our study clarifies that ITPR3 serves as an oncogene in bladder cancer cells and represents a novel candidate for bladder cancer diagnosis and treatment.

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“…4, ITPR3 and CSC markers such as CD44, SOX2 and OCT4 were enriched in BCa stem cells, which indicated that ITPR3 might play a vital role in maintaining the cancer stemness phenotype. We demonstrated that ITPR3 depletion suppressed cancer cell proliferation, migration, invasion and stemness by inhibiting the expression of CD44, which is the main cancer stem cell marker in bladder cancer 39 . NF-κB (nuclear factor (NF)-kappa B) serves as a transcription factor and has been reported to activate various genes, including in ammatory cytokines and oncogenes, which suppress the apoptosis of cancer cells.…”

Section: Discussionmentioning

confidence: 92%

ITPR3 Facilitates Tumor Growth, Metastasis and Stemness by Inducing the NF-ĸB/CD44 Pathway in Urinary Bladder Carcinoma

Zhang

¹

,

Wang

²

,

Yue

³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Bladder carcinoma is one of the most common urological cancers. ITPR3, as a ubiquitous endoplasmic reticulum calcium channel protein, was reported to be involved in the development and progression of various types of cancer. However, the potential roles and molecular mechanism of ITPR3 in bladder cancer are still unclear. Herein, we elucidated a novel role of ITPR3 in regulating the proliferation, metastasis, and stemness of bladder cancer cells.Methods: The expression of ITPR3 in bladder cancer was analyzed using public databases and bladder cancer tissue microarrays. To demonstrate the role of ITPR3 in regulating the NF-ĸB/CD44 pathway and the progression of bladder cancer, a series of molecular biology and biochemistry methods was performed on clinical tissues, along with in vivo and in vitro experiments. The methods used included western blot assay, quantitative RT-PCR assay, immunofluorescence assay, immunohistochemistry (IHC) assays, wound healing assay, Transwell assay, colony formation assay, tumorsphere formation assay, cell flow cytometry analysis, EdU assay, MTT assay, cell transfection, bisulfite sequencing PCR (BSP), a xenograft tumor model and a tail vein cancer metastasis model.Results: Higher ITPR3 expression was found in bladder cancer tissues and bladder cancer cells compared with the corresponding normal peritumor tissues and SV-HUC-1 cells, which was attributed to demethylation in the ITPR3 promoter region. ITPR3 promoted the proliferation of bladder cancer by accelerating cell cycle transformation and promoted local invasion and distant metastasis by inducing epithelial-to-mesenchymal transition (EMT). Meanwhile, ITPR3 maintained the cancer stemness phenotype by regulating CD44 expression. NF-κB, which is upstream of CD44, also played a critical role in this process.Conclusions: Our study clarifies that ITPR3 serves as an oncogene in bladder cancer cells and represents a novel candidate for bladder cancer diagnosis and treatment.

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“…3 , ITPR3 and CSC markers such as CD44, SOX2 and OCT4 were enriched in BCa stem cells, which indicated that ITPR3 might play a vital role in maintaining the cancer stemness phenotype. We demonstrated that ITPR3 depletion suppressed cancer cell proliferation, migration, invasion and stemness by inhibiting the expression of CD44, which is the main cancer stem cell marker in bladder cancer [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-ĸB/CD44 pathway in urinary bladder carcinoma

Zhang

¹

,

Wang

²

,

Yue

³

et al. 2021

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Bladder carcinoma is one of the most common urological cancers. ITPR3, as a ubiquitous endoplasmic reticulum calcium channel protein, was reported to be involved in the development and progression of various types of cancer. However, the potential roles and molecular mechanism of ITPR3 in bladder cancer are still unclear. Herein, we elucidated a novel role of ITPR3 in regulating the proliferation, metastasis, and stemness of bladder cancer cells. Methods The expression of ITPR3 in bladder cancer was analyzed using public databases and bladder cancer tissue microarrays. To demonstrate the role of ITPR3 in regulating the NF-ĸB/CD44 pathway and the progression of bladder cancer, a series of molecular biology and biochemistry methods was performed on clinical tissues, along with in vivo and in vitro experiments. The methods used included western blot assay, quantitative RT-PCR assay, immunofluorescence assay, immunohistochemistry (IHC) assays, wound healing assay, Transwell assay, colony formation assay, tumorsphere formation assay, cell flow cytometry analysis, EdU assay, MTT assay, cell transfection, bisulfite sequencing PCR (BSP), a xenograft tumor model and a tail vein cancer metastasis model. Results Higher ITPR3 expression was found in bladder cancer tissues and bladder cancer cells compared with the corresponding normal peritumor tissues and SV-HUC-1 cells, which was attributed to demethylation in the ITPR3 promoter region. ITPR3 promoted the proliferation of bladder cancer by accelerating cell cycle transformation and promoted local invasion and distant metastasis by inducing epithelial-to-mesenchymal transition (EMT). Meanwhile, ITPR3 maintained the cancer stemness phenotype by regulating CD44 expression. NF-κB, which is upstream of CD44, also played a critical role in this process. Conclusions Our study clarifies that ITPR3 serves as an oncogene in bladder cancer cells and represents a novel candidate for bladder cancer diagnosis and treatment.

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The clinicopathological and prognostic value of CD44 expression in bladder cancer: a study based on meta-analysis and TCGA data

Cited by 22 publications

References 44 publications

ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-ĸB/CD44 pathway in urinary bladder carcinoma

ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-ĸB/CD44 pathway in urinary bladder carcinoma

ITPR3 Facilitates Tumor Growth, Metastasis and Stemness by Inducing the NF-ĸB/CD44 Pathway in Urinary Bladder Carcinoma

ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-ĸB/CD44 pathway in urinary bladder carcinoma

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