KITENIN promotes glioma invasiveness and progression, associated with the induction of EMT and stemness markers
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Kyung-Hwa Lee1,*, Eun-Jung Ahn2,*, Se-Jeong Oh1, Ok Kim1, Young-Eun Joo3, Jeong-A Bae4, Somy Yoon4, Hyang-Hwa Ryu2, Shin Jung2, Kyung-Keun Kim4, Jae-Hyuk Lee1 and Kyung-Sub Moon2
1 Department of Pathology, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do, South Korea
2 Department of Neurosurgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do, South Korea
3 Department of Internal Medicine, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do, South Korea
4 Medical Research Center of Gene Regulation and Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju, South Korea
* These authors contributed equally to this work
Kyung-Sub Moon, email:
Keywords: Neoplastic stem cell, Epithelial-mesenchymal transition, Glioma, Neoplasm invasiveness, Human VANGL1 protein
Received: October 21, 2014 Accepted: December 18, 2014 Published: December 26, 2014
KITENIN (KAI1 COOH-terminal interacting tetraspanin) promotes tumor invasion and metastasis in various cancers. This study assessed the association between KITENIN expression and advanced glioma grade in patients. In vitro assays revealed that KITENIN knockdown inhibited the invasion and migration of glioma cells, whereas KITENIN overexpression promoted their invasion and migration. In orthotopic mouse tumor models, mice transplanted with KITENIN-transfected glioma cells had significantly shorter survival than mice transplanted with mock-transfected cells. Patients with low KITENIN expression showed a significantly longer progression-free survival than patients with high KITENIN expression. KITENIN induced the expression of the epithelial-mesenchymal transition (EMT) markers (N-cadherin, ZEB1, ZEB2, SNAIL and SLUG) as well as the glioma stemness markers (CD133, ALDH1 and EPH-B1). Taken together, these findings showed that high levels of KITENIN increased glioma invasiveness and progression, associated with the up-regulation of EMT and stemness markers.
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