4.3 Article

KITENIN promotes glioma invasiveness and progression, associated with the induction of EMT and stemness markers

Journal

ONCOTARGET
Volume 6, Issue 5, Pages 3240-3253

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3087

Keywords

Neoplastic stem cell; Epithelial-mesenchymal transition; Glioma; Neoplasm invasiveness; Human VANGL1 protein

Funding

  1. Research Institute of Medical Sciences, Chonnam National University [2012-CURIMS-DR004]
  2. National Research Foundation of Korea grant (MRC) [2011-0030132]
  3. National R&D Program for Cancer Control, Ministry of Health Welfare [0720570]
  4. National Research Foundation of Korea [2011-0030132] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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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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