Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
Aging (Albany NY). 2023 May 16;15(10):4182-4201. doi: 10.18632/aging.204721.
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.
细胞外基质 (ECM) 调节与肿瘤发生和发展相关的许多生物学功能；然而，其潜在机制尚不清楚。Sigma 1 受体 (Sig1R) 是一种应激激活的伴侣蛋白，可调节 ECM 与肿瘤细胞之间的串扰，与多种肿瘤的恶性特征有关。然而，在膀胱癌 (BC) 中，Sig1R 过表达与 ECM 之间的联系尚未确定。在这里，我们分析了 Sig1R 和 β-整联蛋白在 BC 细胞中的相互作用及其在 ECM 介导的细胞增殖和血管生成中的作用。我们发现 Sig1R 与 β-整联蛋白形成复合物，促进 ECM 介导的 BC 细胞增殖和血管生成，从而增强肿瘤细胞的侵袭性。这导致生存不良。我们的研究揭示了 Sig1R 介导 BC 细胞与其 ECM 微环境之间的串扰，从而推动了 BC 的进展。有希望的是，通过抑制 Sig1R 靶向离子通道功能可能成为 BC 治疗的一种潜在方法。
