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.
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