Targeting TJP1 attenuates cell–cell aggregation and modulates chemosensitivity against doxorubicin in leiomyosarcoma

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 98; no. 5; pp. 761 - 773
• Main Authors: Lee, Eun-Young, Yu, Jung Yeon, Paek, A Rome, Lee, So Hee, Jang, Hyonchol, Cho, Soo Young, Kim, June Hyuk, Kang, Hyun Guy, Yun, Tak, Oh, Sung Eun, Park, Seog Yun, You, Hye Jin
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2020; Springer Nature B.V
• Subjects: Antibodies; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer therapies; Cell aggregation; Cell culture; Cell interactions; Cell signaling; Doxorubicin; Epithelial cells; Ewings sarcoma; FDA approval; Gefitinib; Gene expression; Growth factors; Human Genetics; Internal Medicine; Liposarcoma; Medical prognosis; Membrane proteins; Molecular Medicine; Multiple myeloma; NF-κB protein; Original Article; Proteins; R&D; Research & development; Research centers; Ribonucleic acid; RNA; Signal transduction; Soft tissue sarcoma; Therapeutic applications; Tumors; TJP1; Soft tissue sarcoma; Chemosensitivity; LMS
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-020-01909-8

Tight junction protein 1 (TJP1) is a membrane-associated cytosolic protein important for cell–cell communication in intercellular barriers in epithelial and non-epithelial cells. Here, we explored the functional involvement of TJP1 in non-epithelial tumors such as soft tissue sarcoma, especially in leiomyosarcoma (LMS). TJP1 expression in soft tissue sarcoma was analyzed in normal and tumor tissues as well as from public datasets such as the TCGA provisional dataset, in which TJP1 expression was compared with other subtypes such as undifferentiated sarcomas, and myxofibrosarcomas. SK-LMS-1 cell lines with reduced TJP1 expression showed attenuated anchorage-independent colony formation as well as reduced intercellular aggregation on non-coated culture plates compared with control as well as parental SK-LMS-1 cells. Transcriptome profiling following TJP1 knockdown in SK-LMS-1 cells suggested the involvement of several signaling pathways, including NF-κB pathway and growth factor receptor signaling. In addition, TJP1 downregulation induced enhanced response against anti-cancer agents, doxorubicin and gefitinib. Taken together, these results suggest that TJP1 contributes to sarcoma genesis and might be useful therapeutic target. Key messages • TJP1 expression at RNA level higher in tumor than in normal tissues of sarcoma. • Targeting TJP1 attenuates cell–cell aggregation and anchorage-independent growth. • Targeting TJP1 is beneficial in anti-cancer therapy in LMS.