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Published on: October 10, 2025
Significance of Tsukushi in lung cancer
Tatsuya Yamada1, Kunimasa Ohta2, Yamato Motooka1
1Departments of Pathology and Experimental Medicine, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan; Thoracic Surgery, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
Objectives:
Tsukushi (TSK), a member of the small leucine-rich repeat proteoglycan (SLRP) family, plays multifunctional roles by interacting with signaling molecules during development. However, the role of TSK in cancer remains unknown. The aim of the present study was to investigate the biological significance of TSK in lung cancer.
Materials And Methods:
Immunohistochemistry of lung cancer tissues and reverse transcription polymerase chain reaction (PCR) of lung cancer cell lines were carried out to detect TSK. Then, RNA sequence analysis, Gene Ontology analysis, quantitative real-time PCR, western blotting, cell counting assay, invasion assays, and xenograft studies were done in a human lung adenocarcinoma cell line, H1975 with modification of TSK expression levels, in order to investigate its biological roles, in particular epithelial-mesenchymal transition (EMT) and proliferation.
Results:
TSK was found to be highly expressed in lung cancer tissues and cell lines. Modification of TSK expression levels in H1975 resulted in changes in molecules related to EMT, including cadherin-1, snail family transcriptional repressor 1, snail family transcriptional repressor 2, and vimentin. The results of cell counting and xenograft assays showed that TSK promotes cell proliferation.
Conclusions:
In lung cancer cells, TSK is expressed more highly than the other SLRPs family members, and regulates the EMT and proliferation. Thus, TSK may be a key coordinator of multiple pathways and an important structural element in the lung cancer microenvironment.
Insights
Tsukushi (TSK) is highly expressed in lung cancer and promotes cell proliferation and epithelial-mesenchymal transition (EMT). TSK may be a key regulator in the lung cancer microenvironment.
Area of Science:
- Oncology
- Molecular Biology
- Proteoglycan Research
Background:
- Tsukushi (TSK) is a small leucine-rich repeat proteoglycan (SLRP) family member with known developmental roles.
- The function of TSK in cancer, particularly lung cancer, has not been previously elucidated.
Purpose of the Study:
- To investigate the biological significance and role of Tsukushi (TSK) in lung cancer.
- To determine if TSK expression correlates with lung cancer progression and affects key cellular processes.
Main Methods:
- TSK expression was analyzed in lung cancer tissues and cell lines using immunohistochemistry and RT-PCR.
- Functional studies involved modifying TSK expression in a human lung adenocarcinoma cell line (H1975) and performing RNA sequencing, Gene Ontology analysis, Western blotting, cell counting, invasion assays, and xenograft studies.
Main Results:
- TSK exhibited high expression in lung cancer tissues and cell lines compared to other SLRPs.
- Altering TSK levels in H1975 cells affected molecules associated with epithelial-mesenchymal transition (EMT), including cadherin-1, snail1, snail2, and vimentin.
- Cell counting and xenograft assays demonstrated that TSK promotes cell proliferation.
Conclusions:
- TSK is significantly upregulated in lung cancer and plays a crucial role in regulating EMT and proliferation.
- TSK may act as a key coordinator of multiple signaling pathways and a significant structural component within the lung cancer microenvironment.
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