溶酶体离子通道 MCOLN2（黏液素-2）通过 IL-1β/NF-κB 通路促进前列腺癌的进展。

Endolysosomal ion channel MCOLN2 (Mucolipin-2) promotes prostate cancer progression via IL-1β/NF-κB pathway.

机构信息

School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China.

出版信息

Br J Cancer. 2021 Nov;125(10):1420-1431. doi: 10.1038/s41416-021-01537-0. Epub 2021 Sep 21.

DOI:10.1038/s41416-021-01537-0

PMID:34548638

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8575885/

Abstract

BACKGROUND

Prostate cancer (Pca) is the most common cancer type among males worldwide. Dysregulation of Ca signaling plays important roles during Pca progression. However, there is lack of information about the role of endolysosomal Ca -permeable channels in Pca progression.

METHODS

The expression pattern of MCOLN2 was studied by immunohistochemistry and western blot. Cell viability assay, transwell assay and in vivo tumorigenesis were performed to evaluate the functional role of MCOLN2. Downstream targets of MCOLN2 were investigated by cytokine array, enzyme-linked immunosorbent assay, Ca release experiments and luciferase reporter assays.

RESULTS

We report that MCOLN2 expression is significantly elevated in Pca tissues, and associated with poor prognosis. Overexpression of MCOLN2 promoted Pca cells proliferation, migration and invasion. Importantly, knockdown of MCOLN2 inhibited Pca xenograft tumor growth and bone lesion development in vivo. In addition, MCOLN2 promoted the production and release of IL-1β. Moreover, luciferase reporter assay and western blot revealed that MCOLN2 promoted Pca development by regulating the IL-1β/NF-κB pathway.

CONCLUSION

In summary, MCOLN2 is crucially involved in Pca progression. Mechanistically, MCOLN2 regulates Pca progression via IL-1β/NF-κB pathway. Our study highlights an intriguing possibility of targeting MCOLN2 as potential therapeutic strategy in Pca treatment.

摘要

背景

前列腺癌（Pca）是全球男性最常见的癌症类型。钙信号的失调在 Pca 的进展中起着重要作用。然而，关于内体溶酶体钙渗透性通道在 Pca 进展中的作用的信息还很缺乏。

方法

通过免疫组织化学和蛋白质印迹研究 MCOLN2 的表达模式。进行细胞活力测定、Transwell 测定和体内肿瘤发生实验，以评估 MCOLN2 的功能作用。通过细胞因子阵列、酶联免疫吸附试验、钙释放实验和荧光素酶报告基因实验研究 MCOLN2 的下游靶点。

结果

我们报告 MCOLN2 的表达在 Pca 组织中显著升高，并与预后不良相关。MCOLN2 的过表达促进了 Pca 细胞的增殖、迁移和侵袭。重要的是，MCOLN2 的敲低抑制了体内 Pca 异种移植物肿瘤的生长和骨病变的发展。此外，MCOLN2 促进了 IL-1β 的产生和释放。此外，荧光素酶报告基因实验和蛋白质印迹显示，MCOLN2 通过调节 IL-1β/NF-κB 通路促进 Pca 的发展。