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STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through
Shunsuke Ohtsuka1, Hisami Kato1, Rei Ishikawa1
1Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
Abstract:
STIL is a regulatory protein essential for centriole biogenesis, and its dysregulation has been implicated in various diseases, including malignancies. However, its role in non-small-cell lung carcinoma (NSCLC) remains unclear. In this study, we examined STIL expression and its potential association with chromosomal numerical abnormalities (CNAs) in NSCLC using The Cancer Genome Atlas (TCGA) dataset, immunohistochemical analysis, and in vitro experiments with NSCLC cell lines designed to overexpress STIL. TCGA data revealed upregulated STIL mRNA expression in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC. Immunohistochemical analysis of cases from our hospital (LUAD, n = 268; LUSC, n = 98) revealed STIL protein overexpression. To elucidate the functional role of STIL, an inducible STIL-overexpressing H1299 NSCLC cell line was generated. Overexpression of STIL in these cells promoted centrosome amplification, leading to chromosomal instability. Finally, analysis of arm-level chromosomal copy number alterations from the TCGA dataset revealed that elevated STIL mRNA expression was associated with CNAs in both LUAD and LUSC. These findings suggest that STIL overexpression is associated with CNAs in NSCLC, likely through centrosome amplification, which is linked to chromosomal instability and might represent a potential therapeutic target for NSCLC treatment.
Insights
STIL protein overexpression in non-small-cell lung carcinoma (NSCLC) correlates with chromosomal abnormalities. This suggests STIL may drive chromosomal instability and offers a potential therapeutic target for NSCLC.
Area of Science:
- Cell Biology
- Cancer Research
- Genetics
Background:
- STIL (Sil) is crucial for centriole biogenesis and its dysregulation is linked to diseases.
- The specific role of STIL in non-small-cell lung carcinoma (NSCLC) is not well understood.
Purpose of the Study:
- To investigate STIL expression in NSCLC.
- To determine the association between STIL and chromosomal numerical abnormalities (CNAs) in NSCLC.
- To explore the functional impact of STIL overexpression in NSCLC.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) dataset for STIL mRNA expression.
- Immunohistochemical analysis of STIL protein in NSCLC patient samples.
- In vitro experiments using NSCLC cell lines with induced STIL overexpression.
Main Results:
- Upregulated STIL mRNA and protein expression were observed in NSCLC subtypes (LUAD, LUSC).
- STIL overexpression in NSCLC cells led to centrosome amplification and chromosomal instability.
- Elevated STIL mRNA levels were associated with chromosomal copy number alterations in NSCLC.
Conclusions:
- STIL overexpression is linked to CNAs in NSCLC, potentially via centrosome amplification.
- STIL-induced chromosomal instability may contribute to NSCLC development.
- STIL represents a potential therapeutic target for NSCLC treatment.
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