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IFITM1作为子宫颈癌细胞表面组动力学和侵袭性表型的调节因子。

IFITM1 as a modulator of surfaceome dynamics and aggressive phenotype in cervical cancer cells.

作者信息

Friedlová Nela, Bortlíková Lucie, Dosedělová Lenka, Uhrík Lukáš, Hupp Ted R, Hernychová Lenka, Vojtěšek Bořivoj, Nekulová Marta

机构信息

Research Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic.

出版信息

Oncol Rep. 2025 Jun;53(6). doi: 10.3892/or.2025.8904. Epub 2025 May 2.

Abstract

Interferon‑induced transmembrane proteins (IFITMs) are frequently overexpressed in cancer cells, including cervical carcinoma cells, and play a role in the progression of various cancer types. However, their mechanisms of action remain incompletely understood. In the present study, by employing a combination of surface membrane protein isolation and quantitative mass spectrometry, it was comprehensively described how the IFITM1 protein influences the composition of the cervical cancer cell surfaceome. Additionally, the effects of interferon‑γ on protein expression and cell surface exposure were evaluated in the presence and absence of IFITM1. The IFITM1‑regulated membrane and membrane‑associated proteins identified are involved mainly in processes such as endocytosis and lysosomal transport, cell‑cell and cell‑extracellular matrix adhesion, antigen presentation and the immune response. To complement the proteomic data, gene expression was analyzed using reverse transcription‑quantitative PCR to distinguish whether the observed changes in protein levels were attributable to transcriptional regulation or differential protein dynamics. Furthermore, the proteomic and gene expression data are supported by functional studies demonstrating the impact of the IFITM1 and IFITM3 proteins on the adhesive, migratory and invasive capabilities of cervical cancer cells, as well as their interactions with immune cells.

摘要

干扰素诱导跨膜蛋白(IFITMs)在癌细胞(包括宫颈癌细胞)中经常过表达,并在多种癌症类型的进展中发挥作用。然而,它们的作用机制仍未完全阐明。在本研究中,通过结合表面膜蛋白分离和定量质谱分析,全面描述了IFITM1蛋白如何影响宫颈癌细胞表面蛋白质组的组成。此外,在有和没有IFITM1的情况下,评估了干扰素-γ对蛋白质表达和细胞表面暴露的影响。鉴定出的受IFITM1调节的膜蛋白和膜相关蛋白主要参与内吞作用和溶酶体运输、细胞-细胞和细胞-细胞外基质粘附、抗原呈递和免疫反应等过程。为补充蛋白质组学数据,使用逆转录定量PCR分析基因表达,以区分观察到的数据水平变化是归因于转录调控还是蛋白质动力学差异。此外,蛋白质组学和基因表达数据得到了功能研究的支持,这些研究证明了IFITM1和IFITM3蛋白对宫颈癌细胞的粘附、迁移和侵袭能力的影响,以及它们与免疫细胞的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b0e/12059461/7a3679852b18/or-53-06-08904-g00.jpg

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