Clostridium perfringens enterotoxin induces claudin-4 to activate YAP in oral squamous cell carcinomas

• DOI: 10.18632/oncotarget.27424
• Publication Date: 2020-01-28T15:28:32Z
• Authors: Chie Nakashima; Kazuhiko Yamamoto; Shingo Kishi; Takamitsu Sasaki; Hitoshi Ohmori; Rina Fujiwara-Tani; Shiori Mori; Isao Kawahara; Yukiko Nishiguchi; Takuya Mori; Masuo Kondoh; Yi Luo; Tadaaki Kirita; Hiroki Kuniyasu
• Keywords: Clostridium perfringens

// Chie Nakashima 1 , 2 Kazuhiko Yamamoto Shingo Kishi Takamitsu Sasaki Hitoshi Ohmori Rina Fujiwara-Tani Shiori Mori Isao Kawahara Yukiko Nishiguchi Takuya Masuo Kondoh 3 Yi Luo 4 Tadaaki Kirita and Hiroki Kuniyasu Department of Molecular Pathology, Nara Medical University, Kashihara, 634-8521, Japan Oral Maxillofacial Surgery, 634-8522, Drug Innovation Center, Graduate School Pharmaceutical Sciences, Osaka Suita, 565-0871, Key Laboratory Neuroregeneration Jiangsu Ministry Education, Co-Innovation Center Neuroregeneration, Nantong Nantong, Province 226001, China Correspondence to: Luo, email: [e-mail] Kirita, [e-mail] Kuniyasu, [e-mail] Keywords: clostridium perfringens enterotoxin; claudin-4; YAP; Hippo signal; oral squamous cell carcinoma; Pathology Received: November 11, 2019 Accepted: December 21, Published: January 28, 2020 ABSTRACT Claudin (CLDN)-4 expression has been associated with malignancy in various cancers. When CLDN4 was examined carcinoma (OSCC), 22 out 57 (39%) cases showed immunoreactivity the nucleus. Nuclear CLDN4-positive a stronger correlation cancer progression than negative cases. Intratumoral anaerobic bacterial DNA examination revealed nuclear 81% Clostridium -positive Treatment human lines HSC3 HSC4 enterotoxin (CPE), induced translocation to enhance epithelial-mesenchymal transition (EMT), stemness, proliferation invasive ability. In addition, CPE treatment suppressed phosphorylation yes-associated protein-1 (YAP1) promoted YAP1 translocation, resulting increased target genes; cyclin D1 connective tissue growth factor. Moreover, it that complex YAP1, zona occludens-2 (ZO-2) formed by treatment, further suppressing LATS1 activating it. Thus YAP activation OSCC regarded important promoting malignant phenotypes. Our research suggested control bacteria may suppress turn tumor progression.