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Research Paper|Volume 15, Issue 10|pp 4182—4201

Sig1R activates extracellular matrix-induced bladder cancer cell proliferation and angiogenesis by combing β-integrin

Feng Zhao1, Tianli Yang1, Liuhua Zhou1, Rongfei Li1, Jingyu Liu1, Jun Zhao1, Ruipeng Jia1
  • 1Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
* Equal contribution
Received: October 25, 2022Accepted: April 15, 2023Published: May 16, 2023
https://doi.org/10.18632/aging.204721

Copyright: © 2023 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The extracellular matrix (ECM) regulates many biological functions involved in tumorigenesis and tumor development; however, the underlying mechanism remains unknown. Sigma 1 receptor (Sig1R), a stress-activated chaperone, regulates the crosstalk between the ECM and tumor cells and is related to the malignant characteristics of several tumors. However, the link between Sig1R overexpression and ECM during malignancy has not been established in bladder cancer (BC).

Here, we analyzed the interaction of Sig1R and β-integrin in BC cells and its role in ECM-mediated cell proliferation and angiogenesis. We found that Sig1R forms a complex with β-integrin to promote ECM-mediated BC cell proliferation and angiogenesis, which enhances the aggressiveness of the tumor cells. This leads to poor survival. Our research revealed that Sig1R mediates the cross-talk between BC cells and their ECM microenvironment, thereby driving the progression of BC. Promisingly, targeting an ion channel function through Sig1R inhibition may serve as a potential approach for BC treatment.