STIM1 promotes cervical cancer progression through autophagy activation via TFEB nuclear translocation

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2024-11-01 DOI:10.1016/j.cellsig.2024.111500

Xi Luo , Mengchan Jian , Ping Wu , Yahua Wu , Yulan Ma , Na Feng , Min Lu , Dandan Shi , Rui Liu , Yan Ding , Wenjun Zhang , Li Fan , Xiju He

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引用次数: 0

Abstract

Background

Autophagy plays an important role in maintaining the stability of intracellular environment, abnormal autophagy is associated with the occurrence and progression of cancer, the role of STIM1 in regulating cancer autophagy remains controversial, and its clinical relevance is unclear. Our study aimed to investigate the effect and mechanism of STIM1 on cervical cancer, thus to provide new molecular therapeutic targets for cervical cancer in clinic.

Methods

We collected CIN III, FIGO IB and IIA fresh Specimens without chemotherapy from patients in Renmin Hospital of Hubei University of Medicine (n = 10). STIM1, TFEB and autophagy related proteins of different stage tissues were detected. In vitro, SKF96365 and AncoA4 were used to inhibit STIM1-administrated Ca²⁺ entry of SiHa cells, Cyclosporine A (calcineurin inhibitors) were used to inhibit CaN/TFEB pathway, Ad-mCherry-GFPLC3B was used to detect autophagy flux, shSTIM1 was used to knockdown STIM1 expression.

Results

The expression levels of STIM1, TFEB and autophagy related proteins were positively correlated with the progression of cervical cancer. Inhibition of STIM1-mediated SOCE can decrease proliferation and migration, and promoted the apoptosis of cervical cancer cells. Knockdown STIM1 can inhibit autophagy and TFEB nuclear translocation.

Conclusion

STIM1 can promote autophagy and accelerate cervical cancer progression by increasing TFEB nuclear translocation of cervical cancer cells.

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STIM1 通过 TFEB 核转位激活自噬，从而促进宫颈癌的进展。

研究背景自噬在维持细胞内环境稳定方面发挥着重要作用，自噬异常与癌症的发生和发展相关，STIM1在调控癌症自噬中的作用仍存在争议，其临床意义尚不明确。我们的研究旨在探讨 STIM1 对宫颈癌的影响及其机制，从而为宫颈癌的临床治疗提供新的分子治疗靶点：方法：我们收集了湖北医药学院附属人民医院未化疗的 CIN III、FIGO IB 和 IIA 新鲜标本（10 例）。检测不同阶段组织的 STIM1、TFEB 和自噬相关蛋白。在体外，用SKF96365和AncoA4抑制STIM1引起的SiHa细胞Ca2+进入，用环孢素A（钙神经蛋白抑制剂）抑制CaN/TFEB通路，用Ad-mCherry-GFPLC3B检测自噬通路，用shSTIM1敲除STIM1的表达：结果：STIM1、TFEB和自噬相关蛋白的表达水平与宫颈癌的进展呈正相关。抑制 STIM1 介导的 SOCE 可减少宫颈癌细胞的增殖和迁移，并促进其凋亡。敲除STIM1可抑制自噬和TFEB核转位：结论：STIM1能促进自噬，并通过增加宫颈癌细胞的TFEB核易位加速宫颈癌的进展。

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

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.