Chai Phei Gan1, Kin Kit Sam1, Pei San Yee1, Nur Syafinaz Zainal1, Bernard Kok Bang Lee1, Zainal Ariff Abdul Rahman2, Vyomesh Patel1, Aik Choon Tan3, Rosnah Binti Zain4, Sok Ching Cheong5,6. 1. Head and Neck Cancer Research Team, Cancer Research Malaysia, 2nd Floor, Outpatient Centre, Subang Jaya Medical Centre, 47500, Subang Jaya, Selangor, Malaysia. 2. Department of Oral & Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia. 3. Division of Medical Oncology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 4. Oral Cancer Research & Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia. 5. Head and Neck Cancer Research Team, Cancer Research Malaysia, 2nd Floor, Outpatient Centre, Subang Jaya Medical Centre, 47500, Subang Jaya, Selangor, Malaysia. sokching.cheong@cancerresearch.my. 6. Department of Oral & Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia. sokching.cheong@cancerresearch.my.
Abstract
PURPOSE: Oral squamous cell carcinoma (OSCC) is a challenging disease to treat. Up to 50% of OSCC patients with advanced disease develop recurrences. Elucidation of key molecular mechanisms underlying OSCC development may provide opportunities to target specific genes and, thus, to improve patient survival. In this study, we examined the expression and functional role of interferon transmembrane protein 3 (IFITM3) in OSCC development. METHODS: The expression of IFITM3 in OSCC and normal oral mucosal tissues was assessed by qRT-PCR and immunohistochemistry. The role of IFITM3 in driving OSCC cell proliferation and survival was examined using siRNA-mediated gene knockdown, and the role of IFITM3 in driving cell cycle regulators was examined using Western blotting. RESULTS: We found that IFITM3 is overexpressed in more than 79% of primary OSCCs. We also found that IFITM3 knockdown led to impaired OSCC cell growth through inhibition of cell proliferation, induction of cell cycle arrest, senescence and apoptosis. In addition, we found that IFITM3 knockdown led to reduced expressions of CCND1 and CDK4 and reduced RB phosphorylation, leading to inhibition of OSCC cell growth. This information may be instrumental for the design of novel targeted therapeutic strategies. CONCLUSIONS: From our data we conclude that IFITM3 is overexpressed in OSCC and may regulate the CCND1-CDK4/6-pRB axis to mediate OSCC cell growth.
PURPOSE:Oral squamous cell carcinoma (OSCC) is a challenging disease to treat. Up to 50% of OSCC patients with advanced disease develop recurrences. Elucidation of key molecular mechanisms underlying OSCC development may provide opportunities to target specific genes and, thus, to improve patient survival. In this study, we examined the expression and functional role of interferon transmembrane protein 3 (IFITM3) in OSCC development. METHODS: The expression of IFITM3 in OSCC and normal oral mucosal tissues was assessed by qRT-PCR and immunohistochemistry. The role of IFITM3 in driving OSCC cell proliferation and survival was examined using siRNA-mediated gene knockdown, and the role of IFITM3 in driving cell cycle regulators was examined using Western blotting. RESULTS: We found that IFITM3 is overexpressed in more than 79% of primary OSCCs. We also found that IFITM3 knockdown led to impaired OSCC cell growth through inhibition of cell proliferation, induction of cell cycle arrest, senescence and apoptosis. In addition, we found that IFITM3 knockdown led to reduced expressions of CCND1 and CDK4 and reduced RB phosphorylation, leading to inhibition of OSCC cell growth. This information may be instrumental for the design of novel targeted therapeutic strategies. CONCLUSIONS: From our data we conclude that IFITM3 is overexpressed in OSCC and may regulate the CCND1-CDK4/6-pRB axis to mediate OSCC cell growth.
Authors: Mitinori Saitou; Bernhard Payer; Ulrike C Lange; Sylvia Erhardt; Sheila C Barton; M Azim Surani Journal: Philos Trans R Soc Lond B Biol Sci Date: 2003-08-29 Impact factor: 6.237
Authors: Paul Shannon; Andrew Markiel; Owen Ozier; Nitin S Baliga; Jonathan T Wang; Daniel Ramage; Nada Amin; Benno Schwikowski; Trey Ideker Journal: Genome Res Date: 2003-11 Impact factor: 9.043
Authors: Young Yang; Jeong-Hyung Lee; Kun Yong Kim; Hyun Keun Song; Jae Kwang Kim; Suk Ran Yoon; Daeho Cho; Kyu Sang Song; Young Ho Lee; Inpyo Choi Journal: Cancer Lett Date: 2005-04-28 Impact factor: 8.679
Authors: Satomi S Tanaka; Go Nagamatsu; Yuko Tokitake; Miyuki Kasa; Patrick P L Tam; Yasuhisa Matsui Journal: Dev Dyn Date: 2004-08 Impact factor: 3.780