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Journal of Experimental & Clinical Cancer Research

Published in:

01-12-2021 | Metastasis | Research

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

Authors: Mengzhao Zhang, Lu Wang, Yangyang Yue, Lu Zhang, Tianjie Liu, Minxuan Jing, Xiao Liang, Minghai Ma, Shan Xu, Ke Wang, Xinyang Wang, Jinhai Fan

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

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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Title: ITPR3 facilitates tumor growth, metastasis and stemness by inducing the NF-ĸB/CD44 pathway in urinary bladder carcinoma
Authors: Mengzhao Zhang
Lu Wang
Yangyang Yue
Lu Zhang
Tianjie Liu
Minxuan Jing
Xiao Liang
Minghai Ma
Shan Xu
Ke Wang
Xinyang Wang
Jinhai Fan
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Metastasis
Bladder Carcinoma
Bladder Carcinoma
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-01866-1

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Abstract

Background

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