STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through Centrosome Amplification
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...
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MDPI AG
2024-12-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/31/12/585 |
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| author | Shunsuke Ohtsuka Hisami Kato Rei Ishikawa Hirofumi Watanabe Ryosuke Miyazaki Shin-ya Katsuragi Katsuhiro Yoshimura Hidetaka Yamada Yasuhiro Sakai Yusuke Inoue Yusuke Takanashi Keigo Sekihara Kazuhito Funai Haruhiko Sugimura Kazuya Shinmura |
| author_facet | Shunsuke Ohtsuka Hisami Kato Rei Ishikawa Hirofumi Watanabe Ryosuke Miyazaki Shin-ya Katsuragi Katsuhiro Yoshimura Hidetaka Yamada Yasuhiro Sakai Yusuke Inoue Yusuke Takanashi Keigo Sekihara Kazuhito Funai Haruhiko Sugimura Kazuya Shinmura |
| author_sort | Shunsuke Ohtsuka |
| collection | DOAJ |
| description | 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, <i>n</i> = 268; LUSC, <i>n</i> = 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. |
| format | Article |
| id | doaj-art-79713bb140f84d2e818ef05f64237f26 |
| institution | DOAJ |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj-art-79713bb140f84d2e818ef05f64237f262025-08-20T02:50:59ZengMDPI AGCurrent Oncology1198-00521718-77292024-12-0131127936794910.3390/curroncol31120585STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through Centrosome AmplificationShunsuke Ohtsuka0Hisami Kato1Rei Ishikawa2Hirofumi Watanabe3Ryosuke Miyazaki4Shin-ya Katsuragi5Katsuhiro Yoshimura6Hidetaka Yamada7Yasuhiro Sakai8Yusuke Inoue9Yusuke Takanashi10Keigo Sekihara11Kazuhito Funai12Haruhiko Sugimura13Kazuya Shinmura14Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Surgery 1, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Surgery 1, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Surgery 1, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanSTIL 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, <i>n</i> = 268; LUSC, <i>n</i> = 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.https://www.mdpi.com/1718-7729/31/12/585centrosome amplificationchromosomal instabilitychromosomal numerical abnormalitylung adenocarcinomalung squamous cell carcinomanon-small-cell lung carcinoma |
| spellingShingle | Shunsuke Ohtsuka Hisami Kato Rei Ishikawa Hirofumi Watanabe Ryosuke Miyazaki Shin-ya Katsuragi Katsuhiro Yoshimura Hidetaka Yamada Yasuhiro Sakai Yusuke Inoue Yusuke Takanashi Keigo Sekihara Kazuhito Funai Haruhiko Sugimura Kazuya Shinmura STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through Centrosome Amplification Current Oncology centrosome amplification chromosomal instability chromosomal numerical abnormality lung adenocarcinoma lung squamous cell carcinoma non-small-cell lung carcinoma |
| title | STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through Centrosome Amplification |
| title_full | STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through Centrosome Amplification |
| title_fullStr | STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through Centrosome Amplification |
| title_full_unstemmed | STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through Centrosome Amplification |
| title_short | STIL Overexpression Is Associated with Chromosomal Numerical Abnormalities in Non-Small-Cell Lung Carcinoma Through Centrosome Amplification |
| title_sort | stil overexpression is associated with chromosomal numerical abnormalities in non small cell lung carcinoma through centrosome amplification |
| topic | centrosome amplification chromosomal instability chromosomal numerical abnormality lung adenocarcinoma lung squamous cell carcinoma non-small-cell lung carcinoma |
| url | https://www.mdpi.com/1718-7729/31/12/585 |
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