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IFITM1 as a modulator of surfaceome dynamics and aggressive phenotype in cervical cancer cells
Nela Friedlová1, Lucie Bortlíková1, Lenka Dosedělová1
1Research Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic.
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.
Insights
Interferon-induced transmembrane proteins (IFITMs) like IFITM1 are overexpressed in cervical cancer. This study reveals how IFITM1 alters the cancer cell surfaceome, impacting adhesion, migration, and immune interactions.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Interferon-induced transmembrane proteins (IFITMs) are implicated in cancer progression, but their precise roles and mechanisms, particularly in cervical carcinoma, are not fully elucidated.
- Overexpression of IFITM proteins is observed in various cancer cells, suggesting a significant contribution to tumorigenesis.
Purpose of the Study:
- To comprehensively characterize the influence of Interferon-induced transmembrane protein 1 (IFITM1) on the cervical cancer cell surfaceome.
- To investigate the effects of interferon-gamma on protein expression and cell surface localization in the presence and absence of IFITM1.
- To explore the functional consequences of IFITM1 and IFITM3 expression on cervical cancer cell behavior and immune cell interactions.
Main Methods:
- Surface membrane protein isolation coupled with quantitative mass spectrometry to profile the cell surfaceome.
- Reverse transcription-quantitative PCR (RT-qPCR) to analyze gene expression and differentiate transcriptional regulation from protein dynamics.
- Functional assays to assess cell adhesion, migration, invasion, and interactions with immune cells.
Main Results:
- IFITM1 significantly alters the composition of the cervical cancer cell surfaceome, identifying key regulated proteins involved in endocytosis, lysosomal transport, cell adhesion, antigen presentation, and immune responses.
- Interferon-gamma modulates protein expression and cell surface exposure differently depending on IFITM1 presence.
- Proteomic and gene expression data correlate with functional studies showing IFITM1 and IFITM3 impact on cervical cancer cell invasiveness and immune cell interactions.
Conclusions:
- IFITM1 plays a crucial role in shaping the cervical cancer cell surfaceome, influencing critical cellular processes and interactions.
- Understanding IFITM1's impact on the surfaceome provides insights into cervical cancer progression and potential therapeutic targets.
- IFITM proteins influence cervical cancer cell malignancy and immune evasion, highlighting their importance in cancer immunology.
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