Skip to main content

Advertisement

SpringerLink
Log in

IFITM3 knockdown reduces the expression of CCND1 and CDK4 and suppresses the growth of oral squamous cell carcinoma cells

  • Original Paper
  • Published:
Cellular Oncology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. P.M. Martensen, J. Justesen, Small ISGs coming forward. J Interf Cytokine Res 24, 1–19 (2004)

    Article  CAS  Google Scholar 

  2. F. Siegrist, M. Ebeling, U. Certa, The small interferon-induced transmembrane genes and proteins. J Interf Cytokine Res 31, 183–197 (2011)

    Article  CAS  Google Scholar 

  3. A.R. Everitt, S. Clare, T. Pertel, S.P. John, R.S. Wash, S.E. Smith, C.R. Chin, E.M. Feeley, J.S. Sims, D.J. Adams, H.M. Wise, L. Kane, D. Goulding, P. Digard, V. Anttila, J.K. Baillie, T.S. Walsh, D.A. Hume, A. Palotie, Y. Xue, V. Colonna, C. Tyler-Smith, J. Dunning, S.B. Gordon, R.L. Smyth, P.J. Openshaw, G. Dougan, A.L. Brass, P. Kellam, IFITM3 restricts the morbidity and mortality associated with influenza. Nature 484, 519–523 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. A.L. Brass, I.C. Huang, Y. Benita, S.P. John, M.N. Krishnan, E.M. Feeley, B.J. Ryan, J.L. Weyer, L. van der Weyden, E. Fikrig, D.J. Adams, R.J. Xavier, M. Farzan, S.J. Elledge, The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 139, 1243–1254 (2009)

    Article  PubMed  PubMed Central  Google Scholar 

  5. S.S. Evans, R.P. Collea, J.A. Leasure, D.B. Lee, IFN-alpha induces homotypic adhesion and Leu-13 expression in human B lymphoid cells. J Immunol 150, 736–747 (1993)

    CAS  PubMed  Google Scholar 

  6. R.A. Smith, J. Young, J.J. Weis, J.H. Weis, Expression of the mouse fragilis gene products in immune cells and association with receptor signaling complexes. Genes Immun 7, 113–121 (2006)

    Article  CAS  PubMed  Google Scholar 

  7. U.C. Lange, M. Saitou, P.S. Western, S.C. Barton, M.A. Surani, The fragilis interferon-inducible gene family of transmembrane proteins is associated with germ cell specification in mice. BMC Dev Biol 3, 1 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. M. Saitou, B. Payer, U.C. Lange, S. Erhardt, S.C. Barton, M.A. Surani, Specification of germ cell fate in mice. Philos Trans R Soc Lond Ser B Biol Sci 358, 1363–1370 (2003)

    Article  CAS  Google Scholar 

  9. S.S. Tanaka, G. Nagamatsu, Y. Tokitake, M. Kasa, P.P. Tam, Y. Matsui, Regulation of expression of mouse interferon-induced transmembrane protein like gene-3, Ifitm3 (mil-1, fragilis), in germ cells. Dev Dyn 230, 651–659 (2004)

    Article  CAS  PubMed  Google Scholar 

  10. S.S. Tanaka, Y.L. Yamaguchi, B. Tsoi, H. Lickert, P.P. Tam, IFITM/Mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primordial germ cell homing and repulsion. Dev Cell 9, 745–756 (2005)

    Article  CAS  PubMed  Google Scholar 

  11. F. Yu, S.S. Ng, B.K. Chow, J. Sze, G. Lu, W.S. Poon, H.F. Kung, M.C. Lin, Knockdown of interferon-induced transmembrane protein 1 (IFITM1) inhibits proliferation, migration, and invasion of glioma cells. J Neuro-Oncol 103, 187–195 (2011)

    Article  CAS  Google Scholar 

  12. B. Zhao, H. Wang, G. Zong, P. Li, The role of IFITM3 in the growth and migration of human glioma cells. BMC Neurol 13, 210 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. H. Hatano, Y. Kudo, I. Ogawa, T. Tsunematsu, A. Kikuchi, Y. Abiko, T. Takata, IFN-induced transmembrane protein 1 promotes invasion at early stage of head and neck cancer progression. Clin Cancer Res 14, 6097–6105 (2008)

    Article  CAS  PubMed  Google Scholar 

  14. D. Zhang, H. Wang, H. He, H. Niu, Y. Li, Interferon induced transmembrane protein 3 regulates the growth and invasion of human lung adenocarcinoma. Thorac Cancer 8, 337–343 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. A.J. Lui, E.S. Geanes, J. Ogony, F. Behbod, J. Marquess, K. Valdez, W. Jewell, O. Tawfik, J. Lewis-Wambi, IFITM1 suppression blocks proliferation and invasion of aromatase inhibitor-resistant breast cancer in vivo by JAK/STAT-mediated induction of p21. Cancer Lett 399, 29–43 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. M. Yang, H. Gao, P. Chen, J. Jia, S. Wu, Knockdown of interferon-induced transmembrane protein 3 expression suppresses breast cancer cell growth and colony formation and affects the cell cycle. Oncol Rep 30, 171–178 (2013)

    Article  CAS  PubMed  Google Scholar 

  17. I.N. Sari, Y.G. Yang, L.T. Phi, H. Kim, M.J. Baek, D. Jeong, H.Y. Kwon, Interferon-induced transmembrane protein 1 (IFITM1) is required for the progression of colorectal cancer. Oncotarget 7, 86039–86050 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  18. F. Yu, D. Xie, S.S. Ng, C.T. Lum, M.Y. Cai, W.K. Cheung, H.F. Kung, G. Lin, X. Wang, M.C. Lin, IFITM1 promotes the metastasis of human colorectal cancer via CAV-1. Cancer Lett 368, 135–143 (2015)

    Article  CAS  PubMed  Google Scholar 

  19. P. Andreu, S. Colnot, C. Godard, P. Laurent-Puig, D. Lamarque, A. Kahn, C. Perret, B. Romagnolo, Identification of the IFITM family as a new molecular marker in human colorectal tumors. Cancer Res 66, 1949–1955 (2006)

    Article  CAS  PubMed  Google Scholar 

  20. J. Fan, Z. Peng, C. Zhou, G. Qiu, H. Tang, Y. Sun, X. Wang, Q. Li, X. Le, K. Xie, Gene-expression profiling in Chinese patients with colon cancer by coupling experimental and bioinformatic genomewide gene-expression analyses: Identification and validation of IFITM3 as a biomarker of early colon carcinogenesis. Cancer 113, 266–275 (2008)

    Article  CAS  PubMed  Google Scholar 

  21. B. Tirosh, V. Daniel-Carmi, L. Carmon, A. Paz, G. Lugassy, E. Vadai, A. Machlenkin, E. Bar-Haim, M.S. Do, I.S. Ahn, M. Fridkin, E. Tzehoval, L. Eisenbach, '1-8 interferon inducible gene family': Putative colon carcinoma-associated antigens. Br J Cancer 97, 1655–1663 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. D. Li, Z. Peng, H. Tang, P. Wei, X. Kong, D. Yan, F. Huang, Q. Li, X. Le, K. Xie, KLF4-mediated negative regulation of IFITM3 expression plays a critical role in colon cancer pathogenesis. Clin Cancer Res 17, 3558–3568 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Y. Jia, M. Zhang, W. Jiang, Z. Zhang, S. Huang, Z. Wang, Overexpression of IFITM3 predicts the high risk of lymphatic metastatic recurrence in pN0 esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy. PeerJ 3, e1355 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  24. D. Borg, C. Hedner, A. Gaber, B. Nodin, R. Fristedt, K. Jirstrom, J. Eberhard, A. Johnsson, Expression of IFITM1 as a prognostic biomarker in resected gastric and esophageal adenocarcinoma. Biomark Res 4, 10 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  25. Y. Yang, J.H. Lee, K.Y. Kim, H.K. Song, J.K. Kim, S.R. Yoon, D. Cho, K.S. Song, Y.H. Lee, I. Choi, The interferon-inducible 9-27 gene modulates the susceptibility to natural killer cells and the invasiveness of gastric cancer cells. Cancer Lett 221, 191–200 (2005)

    Article  CAS  PubMed  Google Scholar 

  26. J. Lee, S.H. Goh, N. Song, J.A. Hwang, S. Nam, I.J. Choi, A. Shin, I.H. Kim, M.H. Ju, J.S. Jeong, Y.S. Lee, Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is regulated by an epigenetic mechanism. Am J Pathol 181, 43–52 (2012)

    Article  CAS  PubMed  Google Scholar 

  27. J. Hu, S. Wang, Y. Zhao, Q. Guo, D. Zhang, J. Chen, J. Li, Q. Fei, Y. Sun, Mechanism and biological significance of the overexpression of IFITM3 in gastric cancer. Oncol Rep 32, 2648–2656 (2014)

    Article  CAS  PubMed  Google Scholar 

  28. T. Hisamatsu, M. Watanabe, H. Ogata, T. Ezaki, S. Hozawa, H. Ishii, T. Kanai, T. Hibi, Interferon-inducible gene family 1-8U expression in colitis-associated colon cancer and severely inflamed mucosa in ulcerative colitis. Cancer Res 59, 5927–5931 (1999)

    CAS  PubMed  Google Scholar 

  29. F. Wu, T. Dassopoulos, L. Cope, A. Maitra, S.R. Brant, M.L. Harris, T.M. Bayless, G. Parmigiani, S. Chakravarti, Genome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies: Insights into distinctive pathogenesis. Inflamm Bowel Dis 13, 807–821 (2007)

    Article  PubMed  Google Scholar 

  30. G.S. Seo, J.K. Lee, J.I. Yu, K.J. Yun, S.C. Chae, S.C. Choi, Identification of the polymorphisms in IFITM3 gene and their association in a Korean population with ulcerative colitis. Exp Mol Med 42, 99–104 (2010)

    Article  CAS  PubMed  Google Scholar 

  31. S. Arora, A. Matta, N.K. Shukla, S.V. Deo, R. Ralhan, Identification of differentially expressed genes in oral squamous cell carcinoma. Mol Carcinog 42, 97–108 (2005)

    Article  CAS  PubMed  Google Scholar 

  32. W. Fang, X. Li, Q. Jiang, Z. Liu, H. Yang, S. Wang, S. Xie, Q. Liu, T. Liu, J. Huang, W. Xie, Z. Li, Y. Zhao, E. Wang, F.M. Marincola, K. Yao, Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of southern China. J Transl Med 6, 32 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. S.C. Cheong, G.V. Chandramouli, A. Saleh, R.B. Zain, S.H. Lau, S. Sivakumaren, R. Pathmanathan, S.S. Prime, S.H. Teo, V. Patel, J.S. Gutkind, Gene expression in human oral squamous cell carcinoma is influenced by risk factor exposure. Oral Oncol 45, 712–719 (2009)

    Article  CAS  PubMed  Google Scholar 

  34. R. Iglesias-Bartolome, D. Martin, J.S. Gutkind, Exploiting the head and neck cancer oncogenome: Widespread PI3K-mTOR pathway alterations and novel molecular targets. Cancer Discov 3, 722–725 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. R.B. Zain, W.M. Ghani, I.A. Razak, R.J. Latifah, A.R. Samsuddin, S.C. Cheong, N. Abdullah, A.R. Ismail, H.B. Hussaini, N.A. Talib, A. Jallaludin, Building partnership in oral cancer research in a developing country: Processes and barriers. Asian Pac J Cancer Prev 10, 513–518 (2009)

    PubMed  Google Scholar 

  36. C.P. Gan, V. Patel, C.M. Mikelis, R.B. Zain, A.A. Molinolo, M.T. Abraham, S.H. Teo, Z.A. Abdul Rahman, J.S. Gutkind, S.C. Cheong, Heterotrimeric G-protein alpha-12 (Galpha12) subunit promotes oral cancer metastasis. Oncotarget 5, 9626–9640 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  37. S.N. Zanaruddin, A. Saleh, Y.H. Yang, S. Hamid, W.M. Mustafa, A.A. Khairul Bariah, R.B. Zain, S.H. Lau, S.C. Cheong, Four-protein signature accurately predicts lymph node metastasis and survival in oral squamous cell carcinoma. Hum Pathol 44, 417–426 (2013)

    Article  CAS  PubMed  Google Scholar 

  38. S. Hamid, K.P. Lim, R.B. Zain, S.M. Ismail, S.H. Lau, W.M. Mustafa, M.T. Abraham, N.A. Nam, S.H. Teo, S.C. Cheong, Establishment and characterization of Asian oral cancer cell lines as in vitro models to study a disease prevalent in Asia. Int J Mol Med 19, 453–460 (2007)

    CAS  PubMed  Google Scholar 

  39. M.Z. Fadlullah, I.K. Chiang, K.R. Dionne, P.S. Yee, C.P. Gan, K.K. Sam, K.H. Tiong, A.K. Ng, D. Martin, K.P. Lim, T.G. Kallarakkal, W.M. Mustafa, S.H. Lau, M.T. Abraham, R.B. Zain, Z.A. Rahman, A. Molinolo, V. Patel, J.S. Gutkind, A.C. Tan, S.C. Cheong, Genetically-defined novel oral squamous cell carcinoma cell lines for the development of molecular therapies. Oncotarget 7, 27802–27818 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  40. C.P. Gan, S. Hamid, S.Y. Hor, R.B. Zain, S.M. Ismail, W.M. Wan Mustafa, S.H. Teo, N. Saunders, S.C. Cheong, Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence. Head Neck 34, 344–353 (2012)

    Article  PubMed  Google Scholar 

  41. D. Szklarczyk, J.H. Morris, H. Cook, M. Kuhn, S. Wyder, M. Simonovic, A. Santos, N.T. Doncheva, A. Roth, P. Bork, L.J. Jensen, C. von Mering, The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res 45, D362–D368 (2017)

    Article  CAS  PubMed  Google Scholar 

  42. P. Shannon, A. Markiel, O. Ozier, N.S. Baliga, J.T. Wang, D. Ramage, N. Amin, B. Schwikowski, T. Ideker, Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res 13, 2498–2504 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. A. Eldar, H. Rozenberg, Y. Diskin-Posner, R. Rohs, Z. Shakked, Structural studies of p53 inactivation by DNA-contact mutations and its rescue by suppressor mutations via alternative protein-DNA interactions. Nucleic Acids Res 41, 8748–8759 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. H. Lickert, B. Cox, C. Wehrle, M.M. Taketo, R. Kemler, J. Rossant, Dissecting Wnt/beta-catenin signaling during gastrulation using RNA interference in mouse embryos. Development 132, 2599–2609 (2005)

    Article  CAS  PubMed  Google Scholar 

  45. M. Nagasawa, E.W. Gelfand, J.J. Lucas, Accumulation of high levels of the p53 and p130 growth-suppressing proteins in cell lines stably over-expressing cyclin-dependent kinase 6 (cdk6). Oncogene 20, 2889–2899 (2001)

    Article  CAS  PubMed  Google Scholar 

  46. K. Kollmann, G. Heller, C. Schneckenleithner, W. Warsch, R. Scheicher, R.G. Ott, M. Schafer, S. Fajmann, M. Schlederer, A.I. Schiefer, U. Reichart, M. Mayerhofer, C. Hoeller, S. Zochbauer-Muller, D. Kerjaschki, C. Bock, L. Kenner, G. Hoefler, M. Freissmuth, A.R. Green, R. Moriggl, M. Busslinger, M. Malumbres, V. Sexl, A kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis. Cancer Cell 30, 359–360 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. J.J. Lucas, J. Domenico, E.W. Gelfand, Cyclin-dependent kinase 6 inhibits proliferation of human mammary epithelial cells. Mol Cancer Res 2, 105–114 (2004)

    CAS  PubMed  Google Scholar 

  48. C.R. Pickering, J. Zhang, S.Y. Yoo, L. Bengtsson, S. Moorthy, D.M. Neskey, M. Zhao, M.V. Ortega Alves, K. Chang, J. Drummond, E. Cortez, T.X. Xie, D. Zhang, W. Chung, J.P. Issa, P.A. Zweidler-McKay, X. Wu, A.K. El-Naggar, J.N. Weinstein, J. Wang, D.M. Muzny, R.A. Gibbs, D.A. Wheeler, J.N. Myers, M.J. Frederick, Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov 3, 770–781 (2013)

    Article  CAS  PubMed  Google Scholar 

  49. T.N. Beck, E.A. Golemis, Genomic insights into head and neck cancer. Cancers of the head & neck 1, (2016). https://doi.org/10.1186/s41199-016-0003-z

  50. T.C.G.A. Network, M.S. Lawrence, C. Sougnez, L. Lichtenstein, K. Cibulskis, E. Lander, S.B. Gabriel, G. Getz, A. Ally, M. Balasundaram, I. Birol, R. Bowlby, D. Brooks, Y.S.N. Butterfield, R. Carlsen, D. Cheng, A. Chu, N. Dhalla, R. Guin, R.A. Holt, S.J.M. Jones, D. Lee, H.I. Li, M.A. Marra, M. Mayo, R.A. Moore, A.J. Mungall, A.G. Robertson, J.E. Schein, P. Sipahimalani, A. Tam, N. Thiessen, T. Wong, A. Protopopov, N. Santoso, S. Lee, M. Parfenov, J. Zhang, H.S. Mahadeshwar, J. Tang, X. Ren, S. Seth, P. Haseley, D. Zeng, L. Yang, A.W. Xu, X. Song, A. Pantazi, C.A. Bristow, A. Hadjipanayis, J. Seidman, L. Chin, P.J. Park, R. Kucherlapati, R. Akbani, T. Casasent, W. Liu, Y. Lu, G. Mills, T. Motter, J. Weinstein, L. Diao, J. Wang, Y.H. Fan, J. Liu, K. Wang, J.T. Auman, S. Balu, T. Bodenheimer, E. Buda, D.N. Hayes, K.A. Hoadley, A.P. Hoyle, S.R. Jefferys, C.D. Jones, P.K. Kimes, Y. Liu, J.S. Marron, S. Meng, P.A. Mieczkowski, L.E. Mose, J.S. Parker, C.M. Perou, J.F. Prins, J. Roach, Y. Shi, J.V. Simons, D. Singh, M.G. Soloway, D. Tan, U. Veluvolu, V. Walter, S. Waring, M.D. Wilkerson, J. Wu, N. Zhao, A.D. Cherniack, P.S. Hammerman, A.D. Tward, C.S. Pedamallu, G. Saksena, J. Jung, A.I. Ojesina, S.L. Carter, T.I. Zack, S.E. Schumacher, R. Beroukhim, S.S. Freeman, M. Meyerson, J. Cho, L. Chin, G. Getz, M.S. Noble, D. DiCara, H. Zhang, D.I. Heiman, N. Gehlenborg, D. Voet, P. Lin, S. Frazer, P. Stojanov, Y. Liu, L. Zou, J. Kim, C. Sougnez, S.B. Gabriel, M.S. Lawrence, D. Muzny, H. Doddapaneni, C. Kovar, J. Reid, D. Morton, Y. Han, W. Hale, H. Chao, K. Chang, J.A. Drummond, R.A. Gibbs, N. Kakkar, D. Wheeler, L. Xi, G. Ciriello, M. Ladanyi, W. Lee, R. Ramirez, C. Sander, R. Shen, R. Sinha, N. Weinhold, B.S. Taylor, B.A. Aksoy, G. Dresdner, J. Gao, B. Gross, A. Jacobsen, B. Reva, N. Schultz, S.O. Sumer, Y. Sun, T.A. Chan, L.G. Morris, J. Stuart, S. Benz, S. Ng, C. Benz, C. Yau, S.B. Baylin, L. Cope, L. Danilova, J.G. Herman, M. Bootwalla, D.T. Maglinte, P.W. Laird, T. Triche Jr., D.J. Weisenberger, D.J. Van Den Berg, N. Agrawal, J. Bishop, P.C. Boutros, J.P. Bruce, L.A. Byers, J. Califano, T.E. Carey, Z. Chen, H. Cheng, S.I. Chiosea, E. Cohen, B. Diergaarde, A.M. Egloff, A.K. El-Naggar, R.L. Ferris, M.J. Frederick, J.R. Grandis, Y. Guo, R.I. Haddad, P.S. Hammerman, T. Harris, D.N. Hayes, A.B.Y. Hui, J.J. Lee, S.M. Lippman, F.-F. Liu, J.B. McHugh, J. Myers, P.K.S. Ng, B. Perez-Ordonez, C.R. Pickering, M. Prystowsky, M. Romkes, A.D. Saleh, M.A. Sartor, R. Seethala, T.Y. Seiwert, H. Si, A.D. Tward, C. Van Waes, D.M. Waggott, M. Wiznerowicz, W.G. Yarbrough, J. Zhang, Z. Zuo, K. Burnett, D. Crain, J. Gardner, K. Lau, D. Mallery, S. Morris, J. Paulauskis, R. Penny, C. Shelton, T. Shelton, M. Sherman, P. Yena, A.D. Black, J. Bowen, J. Frick, J.M. Gastier-Foster, H.A. Harper, K. Leraas, T.M. Lichtenberg, N.C. Ramirez, L. Wise, E. Zmuda, J. Baboud, M.A. Jensen, A.B. Kahn, T.D. Pihl, D.A. Pot, D. Srinivasan, J.S. Walton, Y. Wan, R.A. Burton, T. Davidsen, J.A. Demchok, G. Eley, M.L. Ferguson, K.R.M. Shaw, B.A. Ozenberger, M. Sheth, H.J. Sofia, R. Tarnuzzer, Z. Wang, L. Yang, J.C. Zenklusen, C. Saller, K. Tarvin, C. Chen, R. Bollag, P. Weinberger, W. Golusiński, P. Golusiński, M. Ibbs, K. Korski, A. Mackiewicz, W. Suchorska, B. Szybiak, M. Wiznerowicz, K. Burnett, E. Curley, J. Gardner, D. Mallery, R. Penny, T. Shelton, P. Yena, C. Beard, C. Mitchell, G. Sandusky, N. Agrawal, J. Ahn, J. Bishop, J. Califano, Z. Khan, J.P. Bruce, A.B.Y. Hui, J. Irish, F.-F. Liu, B. Perez-Ordonez, J. Waldron, P.C. Boutros, D.M. Waggott, J. Myers, W.N. William Jr., S.M. Lippman, S. Egea, C. Gomez-Fernandez, L. Herbert, C.R. Bradford, T.E. Carey, D.B. Chepeha, A.S. Haddad, T.R. Jones, C.M. Komarck, M. Malakh, J.B. McHugh, J.S. Moyer, A. Nguyen, L.A. Peterson, M.E. Prince, L.S. Rozek, M.A. Sartor, E.G. Taylor, H.M. Walline, G.T. Wolf, L. Boice, B.S. Chera, W.K. Funkhouser, M.L. Gulley, T.G. Hackman, D.N. Hayes, M.C. Hayward, M. Huang, W.K. Rathmell, A.H. Salazar, W.W. Shockley, C.G. Shores, L. Thorne, M.C. Weissler, S. Wrenn, A.M. Zanation, S.I. Chiosea, B. Diergaarde, A.M. Egloff, R.L. Ferris, M. Romkes, R. Seethala, B.T. Brown, Y. Guo, M. Pham, W.G. Yarbrough, Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517, 576–582 (2015)

    Article  CAS  Google Scholar 

  51. L. Michel, J. Ley, T.M. Wildes, A. Schaffer, A. Robinson, S.E. Chun, W. Lee, J. Lewis Jr., K. Trinkaus, D. Adkins, Phase I trial of palbociclib, a selective cyclin dependent kinase 4/6 inhibitor, in combination with cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Oral Oncol 58, 41–48 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We would like to thank all consented patients who participated in this study. This study was funded by Ministry of Science, Technology and Innovation (MOSTI 06-00-00-0000), University of Malaya (UM.C/625/1/HIR/MOHE/DENT-03) and sponsors of Cancer Research Malaysia. Cancer Research Malaysia is a non-profit research organization. We are committed to an understanding of cancer prevention, diagnosis and treatment through a fundamental research program.

Author information

Authors and Affiliations

  1. Head and Neck Cancer Research Team, Cancer Research Malaysia, 2nd Floor, Outpatient Centre, Subang Jaya Medical Centre, 47500, Subang Jaya, Selangor, Malaysia

    Chai Phei Gan, Kin Kit Sam, Pei San Yee, Nur Syafinaz Zainal, Bernard Kok Bang Lee, Vyomesh Patel & Sok Ching Cheong

  2. Department of Oral & Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia

    Zainal Ariff Abdul Rahman & Sok Ching Cheong

  3. Division of Medical Oncology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Aik Choon Tan

  4. Oral Cancer Research & Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia

    Rosnah Binti Zain

Authors
  1. Chai Phei Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kin Kit Sam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pei San Yee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nur Syafinaz Zainal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bernard Kok Bang Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zainal Ariff Abdul Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vyomesh Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Aik Choon Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rosnah Binti Zain
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sok Ching Cheong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sok Ching Cheong.

Ethics declarations

Conflict of interest

All authors declared that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Supplementary fig. 1

mRNA expression of IFITM family members in head and neck cancer in TCGA database (PNG 2550 kb)

High Resolution Image (TIF 654 kb)

Supplementary fig. 2

(a) Endogenous expression of IFITM3 in oral cancer cell lines. (b&c) Specific IFITM3 knockdown by si18 determined by qRT-PCR analysis (PNG 529 kb)

High Resolution Image (TIF 1014 kb)

Supplementary fig. 3

Microscopic view of cells after transfection with si18. Morphological changes and floating cells are apparent after IFITM3 knockdown compared to that in NT siRNA cells. (b) Microscopic view of soft agar assay comparing IFITM3 knockdown cells with NT siRNA cells (PNG 1537 kb)

High Resolution Image (TIF 2343 kb)

Supplementary Table 1

(DOCX 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gan, C.P., Sam, K.K., Yee, P.S. et al. IFITM3 knockdown reduces the expression of CCND1 and CDK4 and suppresses the growth of oral squamous cell carcinoma cells. Cell Oncol. 42, 477–490 (2019). https://doi.org/10.1007/s13402-019-00437-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13402-019-00437-z

Keywords

Search

Navigation