RIPK2 and lysosomal pathway: Unveiling a new mechanism for lung cancer metastasis

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-11-08 DOI:10.1016/j.tranon.2024.102182

Wei Liu , Wei Xu , Hui Hao , Lin Yang , Bo Zhang , Yan Zhang

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引用次数: 0

Abstract

Background

This study aims to explore the role of RIPK2 in lung cancer metastasis and its potential mechanisms.

Methods

The expression levels of RIPK2 in lung cancer patients and cell lines were detected by immunohistochemistry, qRT-PCR, and Western blot. RIPK2 expression was knocked down using siRNA technology, and its effects on the proliferation, migration, and invasion capabilities of lung cancer cells were assessed through CCK-8, EdU, colony formation, and Transwell assays. Furthermore, by overexpressing RIPK2 and LAMP2, the regulatory effect of RIPK2 on the lysosomal pathway and its mechanism of action in lung cancer metastasis were investigated.

Results

The results showed that the expression of RIPK2 was significantly increased in lung cancer patients and cell lines. Knockdown of RIPK2 significantly inhibited the migration, invasion, and proliferation capabilities of lung cancer cells, while overexpression of RIPK2 promoted these malignant behaviors. Further studies found that RIPK2 promoted lung cancer metastasis by inhibiting LAMP2 expression, thereby suppressing the lysosomal pathway and altering the tumor microenvironment. Additionally, overexpression of LAMP2 could reverse the promotive effects of RIPK2 overexpression on the malignant behaviors of lung cancer cells.

Conclusion

This study reveals for the first time that RIPK2 promotes lung cancer metastasis by inhibiting LAMP2 expression, thereby suppressing the lysosomal pathway and altering the tumor microenvironment. In the future, targeted therapy against RIPK2 and LAMP2 may become an effective means to inhibit lung cancer metastasis.

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RIPK2和溶酶体途径：揭示肺癌转移的新机制

背景：本研究旨在探讨RIPK2在肺癌转移中的作用及其潜在机制：本研究旨在探讨 RIPK2 在肺癌转移中的作用及其潜在机制：方法：通过免疫组化、qRT-PCR和Western blot检测RIPK2在肺癌患者和细胞株中的表达水平。利用 siRNA 技术敲除 RIPK2 的表达，并通过 CCK-8、EdU、集落形成和 Transwell 试验评估其对肺癌细胞增殖、迁移和侵袭能力的影响。此外，通过过表达 RIPK2 和 LAMP2，研究了 RIPK2 对溶酶体通路的调控作用及其在肺癌转移中的作用机制：结果表明，RIPK2在肺癌患者和细胞系中的表达明显增加。结果：研究结果表明，RIPK2 在肺癌患者和细胞株中的表达明显增加，敲除 RIPK2 能明显抑制肺癌细胞的迁移、侵袭和增殖能力，而过表达 RIPK2 则会促进这些恶性行为。进一步的研究发现，RIPK2 通过抑制 LAMP2 的表达，从而抑制溶酶体通路并改变肿瘤微环境，促进肺癌转移。此外，LAMP2的过表达可以逆转RIPK2过表达对肺癌细胞恶性行为的促进作用：本研究首次揭示了RIPK2通过抑制LAMP2的表达，从而抑制溶酶体通路并改变肿瘤微环境来促进肺癌转移。未来，针对RIPK2和LAMP2的靶向治疗可能成为抑制肺癌转移的有效手段。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.