Stiffness-related stress granules promote the metastasis of early-stage oral squamous cell carcinoma via anoikis resistance.

IF 4.8 2区医学 Q2 CELL BIOLOGY

Cellular Oncology Pub Date : 2026-04-20 DOI:10.1007/s13402-026-01198-2

Hong Jiang, Kan Li, Yahui Wang, Qiuhan Zheng, Huanzi Lu, Dikan Wang, Jianghai Chen, Guiqing Liao, Yujie Liang

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引用次数: 0

Abstract

Background: Surgery is the first choice of treatment for oral squamous cell carcinoma (OSCC), including primary tumor resection and neck dissection. However, neck dissection of early-stage OSCC patients is still controversial. Exploration of mechanisms of early-stage OSCC metastasis might help to guide treatment choice. Our previous research has demonstrated that matrix stiffness activated the PERK-associated unfolded protein response (UPR), thereby contributing to early-stage OSCC metastasis. Since stress granules (SGs) are also regulated by PERK-mediated UPR, our study aimed to identify stiffness-related SGs and decipher their function of modulating early-stage OSCC metastasis.

Methods: At first, we evaluated matrix stiffness and SGs level in early-stage OSCC tissues. Then enhanced matrix stiffness was simulated in vivo and its effect on metastasis and SGs expression was observed. Furthermore, A force loading model was adopted to identify the stiffness-related SGs in vitro and the effects of stiffness-related SGs on metastasis were further evaluated in vitro and in vivo. We identified the unique type of SGs which was stiffness-related to adopt mechanical stimuli. The stiffness-related SGs may boost metastasis cascade through promotion of anoikis resistance. At last, we investigated the containing mRNAs of stiffness-related SGs through RNA Immunoprecipitation Sequencing.

Results: The stiffness-related SGs were identified which may boost metastasis cascade through promotion of anoikis resistance. The unique SGs were rich in mRNA related to negative regulation of apoptosis, partly explained the anoikis resistance associated with stiffness-related SGs.

Conclusions: The stiffness-related SGs may protect the disseminated cancer cells from anoikis resistance by harboring the set of specific mRNAs. Matrix stiffness promotes the formation of SGs in OSCC, getting prepared for metastasis in the early stage.

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刚度相关的应力颗粒通过anoikis抵抗促进早期口腔鳞状细胞癌的转移。

背景：手术是口腔鳞状细胞癌（OSCC）的首选治疗方法，包括原发肿瘤切除和颈部清扫。然而，早期OSCC患者的颈部清扫术仍存在争议。探讨早期OSCC转移机制有助于指导治疗选择。我们之前的研究表明，基质硬度激活了perk相关的未折叠蛋白反应（UPR），从而促进了早期OSCC转移。由于应力颗粒（SGs）也受perk介导的UPR调节，因此我们的研究旨在鉴定与刚度相关的SGs，并解读其调节早期OSCC转移的功能。方法：我们首先评估早期OSCC组织的基质刚度和SGs水平。然后在体内模拟增强基质刚度，观察其对转移和SGs表达的影响。此外，采用力加载模型对体外刚度相关SGs进行鉴定，并进一步在体外和体内评估刚度相关SGs对转移的影响。我们确定了独特类型的SGs，这是刚性相关的，采用机械刺激。刚性相关的SGs可能通过促进anoikis的抗性来促进转移级联。最后，我们通过RNA免疫沉淀测序研究了刚性相关SGs中含有的mrna。结果：鉴定出与刚性相关的SGs，其可能通过促进anoikis耐药性而促进转移级联。独特的SGs富含与细胞凋亡负调控相关的mRNA，这在一定程度上解释了与刚度相关SGs相关的anoikis抗性。结论：刚性相关的SGs可能通过携带一组特异性mrna来保护播散性癌细胞免受anoikis的耐药。基质刚度促进基底细胞癌中SGs的形成，为早期转移做好准备。

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 Oncology ONCOLOGY-CELL BIOLOGY

CiteScore

10.30

自引率

1.50%

发文量

审稿时长

12 months

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.