Oncotarget

Research Papers:

CD44 exerts a functional role during EMT induction in cisplatin-resistant head and neck cancer cells

Hiroaki Miyazaki _, Ryou-u Takahashi, Marta Prieto-Vila, Yumi Kawamura, Seiji Kondo, Tatsuo Shirota and Takahiro Ochiya

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Oncotarget. 2018; 9:10029-10041. https://doi.org/10.18632/oncotarget.24252

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Abstract

Hiroaki Miyazaki1,2, Ryou-u Takahashi1, Marta Prieto-Vila1, Yumi Kawamura1,3, Seiji Kondo2, Tatsuo Shirota2 and Takahiro Ochiya1

1Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo 104-0045, Japan

2Department of Oral and Maxillofacial Surgery, Showa University School of Dentistry, Tokyo 145-8515, Japan

3Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba 1-1-1 Tennodai, Ibaraki 305-8577, Japan

Correspondence to:

Takahiro Ochiya, email: [email protected]

Keywords: oral cancer, CD44, EMT, cancer stem cell niche

Received: January 12, 2017     Accepted: August 31, 2017     Published: January 13, 2018

ABSTRACT

A number of studies report that epithelial to mesenchymal transition (EMT) supports the generation and maintenance of cancer stem cells (CSCs), which show tumor seeding ability and drug resistance; however, the molecular mechanisms underlying induction of EMT-associated tumor malignancy remain unclear. The present study reports that oral cancer cells switch from expressing the CD44 variant form (CD44v) to expressing the standard form (CD44s) during acquisition of cisplatin-resistance, which resulted in EMT induction. CD44s induced an EMT phenotype in cisplatin resistant cells by up-regulating ZEB1, a transcriptional repressor of E-cadherin. More importantly, CD44s up-regulated ZEB1 by suppressing microRNA-200c, which is a non-coding RNA that directly represses the ZEB1 gene. These results demonstrate the importance of the association between platinum resistance and CD44s during EMT induction in oral cancer cells.


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