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UFM1 对 PLAC8 的修饰通过影响三阴性乳腺癌中 PD-L1 水平来影响肿瘤增殖和免疫反应。

Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer.

机构信息

Department of Surgical Oncology, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Zhejiang, Hangzhou, China.

Zhejiang university, Zhejiang, Hangzhou, China.

出版信息

J Immunother Cancer. 2022 Dec;10(12). doi: 10.1136/jitc-2022-005668.

DOI:10.1136/jitc-2022-005668
PMID:36543379
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9772693/
Abstract

BACKGROUND

Triple-negative breast cancer is characterized by a poor prognosis and lack of targeted treatments, and thus, new targeting markers and therapeutic strategies are urgently needed. We previously indicated that PLAC8 promotes tumorigenesis and exerts multidrug resistance in breast cancer. Therefore, we aimed to characterize the PLAC8-regulated network in triple-negative breast cancer.

METHODS

We measured the levels of PLAC8 in breast cancer cell lines and found that PLAC8 is post-translationally modified by ubiquitin-fold modifier 1 (UFM1). Then, we revealed a new regulatory system of PD-L1 by PLAC8 in triple-negative breast cancer. We also tested the molecular functions of PLAC8 in triple-negative breast cancer cell lines and measured the expression of PLAC8 and PD-L1 in breast cancer tissues.

RESULTS

PLAC8 was generally highly expressed in triple-negative breast cancer and could be modified by UFM1, which maintains PLAC8 protein stability. Moreover, PLAC8 could promote cancer cell proliferation and affect the immune response by regulating the level of PD-L1 ubiquitination. Additionally, among patients with breast cancer, the expression of PLAC8 was higher in triple-negative breast cancer than in non-triple-negative breast cancer and positively correlated with the level of PD-L1.

CONCLUSIONS

Our current study discoveries a new PLAC8-regulated network in triple-negative breast cancer and provides corresponding guidance for the clinical diagnosis and immunotherapy of triple-negative breast cancer.

摘要

背景

三阴性乳腺癌的预后较差，缺乏靶向治疗，因此急需新的靶向标志物和治疗策略。我们之前表明 PLAC8 促进乳腺癌的肿瘤发生并发挥多药耐药作用。因此，我们旨在表征三阴性乳腺癌中 PLAC8 调节的网络。

方法

我们测量了乳腺癌细胞系中 PLAC8 的水平，发现 PLAC8 被泛素样修饰酶 1（UFM1）翻译后修饰。然后，我们揭示了 PLAC8 在三阴性乳腺癌中的 PD-L1 的新调控系统。我们还在三阴性乳腺癌细胞系中测试了 PLAC8 的分子功能，并测量了乳腺癌组织中 PLAC8 和 PD-L1 的表达。

结果

PLAC8 在三阴性乳腺癌中普遍高表达，并且可以被 UFM1 修饰，从而维持 PLAC8 蛋白的稳定性。此外，PLAC8 可以通过调节 PD-L1 泛素化水平促进癌细胞增殖并影响免疫反应。此外，在乳腺癌患者中，PLAC8 的表达在三阴性乳腺癌中高于非三阴性乳腺癌，并且与 PD-L1 的水平呈正相关。

结论

我们目前的研究在三阴性乳腺癌中发现了一个新的 PLAC8 调节网络，并为三阴性乳腺癌的临床诊断和免疫治疗提供了相应的指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/b78f724a389b/jitc-2022-005668f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/c3c736040521/jitc-2022-005668f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/0acda08d744b/jitc-2022-005668f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/e797f6236ef4/jitc-2022-005668f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/da67ceba74d1/jitc-2022-005668f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/72a8e80410d4/jitc-2022-005668f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/fa4e328acf34/jitc-2022-005668f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/b78f724a389b/jitc-2022-005668f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/c3c736040521/jitc-2022-005668f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/0acda08d744b/jitc-2022-005668f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/e797f6236ef4/jitc-2022-005668f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/da67ceba74d1/jitc-2022-005668f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/72a8e80410d4/jitc-2022-005668f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/fa4e328acf34/jitc-2022-005668f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/9772693/b78f724a389b/jitc-2022-005668f07.jpg

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