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Withaferin A mitigates metastatic traits in human oral squamous cell carcinoma caused by aberrant claudin-1 expression |
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| Authors: | Shin Ji-Ae Kim Lee-Han Ryu Mi Heon Choi So-Young Jin Bohwan Lee WonWoo Jung Yun Chan Ahn Chi-Hyun Ahn Min-Hye Hong Kyoung-Ok Swarup Neeti Chawla Kunal Kang Se Chan Hong Seong Doo Cho Sung-Dae |
| Affiliation: | 1.Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 03080, Republic of Korea ;2.Department of Microbiology, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea ;3.Department of Oral Pathology, School of Dentistry, Yangsan Campus of Pusan National University, Yangsan, 50612, Republic of Korea ;4.Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Daegu, 41940, Republic of Korea ;5.Laboratory Animal Center, CHA University, CHA Biocomplex, Sampyeong-dong, Seongnam, 13488, Republic of Korea ;6.Chaon, 301-3, 240, Pangyoyeok-ro, Bundang-gu, Seongnam, 13493, Republic of Korea ;7.Computer Science School of Interactive Computing Georgia Institute of Technology, 756 West Peachtree Street, Atlanta, GA, 30332, USA ;8.Graduate School of Biotechnology and Department of Oriental Medicinal Biotechnology, Kyung Hee University, Yongin, 17104, Republic of Korea ; |
| Abstract: | Abnormal expression of claudin-1 (CLDN1) has important roles in carcinogenesis and metastasis in various cancers. The role of CLDN1 in human oral squamous cell carcinoma (OSCC) remains unknown. Here, we report the functional role of CLDN1 in metastasis of human OSCC, as a potential target regulated by withaferin A. From gene expression profiling with microarray technology, we found that the majority of notable differentially expressed genes were classified into migration/invasion category. Withaferin A impaired the motility of human OSCC cells in vitro and suppressed metastatic nodule formation in an in vivo metastasis model, both associated with reduced CLDN1. CLDN1 overexpression enhanced metastatic nodule formation in vivo, resulting in severe metastatic lesions in lung tissue. Moreover, CLDN1 expression was positively correlated to lymphatic metastasis in OSCC patients. The impaired motility of human OSCC cells upon withaferin A treatment was restored by CLDN1 overexpression. Furthermore, upregulation of let-7a induced by withaferin A was inversely correlated to CLDN1 expression. Overall, these give us an insight into the function of CLDN1 for prognosis and treatment of human OSCC, substantiating further investigation into the use of withaferin A as good anti-metastatic drug candidate. Graphical abstract |
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