Effect of EPHB6 knockdown on migration, invasion, and tumorigenicity of oral cancer cells in vitro

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Introduction. In recent years, a rising incidence of oral cancer (OC) has been observed among young adults without traditional risk factors (smoking, alcohol consumption, and human papillomavirus infection). An aggressive clinical course and a high recurrence rate are observed in patients of this age group. Therefore, there is a growing need to identify novel molecular alterations that could elucidate the mechanisms driving the disease progression. Previously, we identified mutations in the EPHB6 gene associated with early-onset OC recurrence.

Aim. To evaluate the effect of EPHB6 knockdown on the functional characteristics of OC cells in vitro.

Materials and methods. The OC cell line Cal-27 was used in this study. Gene knockdown was induced using small interfering RNAs.

Results. EPHB6 knockdown resulted in a 90 % reduction in gene expression relative to the control, which was accompanied by alterations in cellular functional properties, including inhibition of migration and invasion, as well as reduced tumorigenic capacity in three-dimensional cultures.

Conclusion. These findings shed light on the potential mechanisms by which EPHB6 contributes to early-onset OC progression.

About the authors

Maria S. Tretyakova

Tomsk National Research Medical Center of the Russian Academy of Sciences

Author for correspondence.
Email: trremar@mail.ru
ORCID iD: 0000-0002-5040-931X

Cancer Research Institute

Russian Federation, 5 Kooperativny Lаne, Tomsk 634009

E. S. Kolegova

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: trremar@mail.ru
ORCID iD: 0000-0001-9122-3274

Cancer Research Institute

Russian Federation, 5 Kooperativny Lаne, Tomsk 634009

E. A. Prostakishina

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: trremar@mail.ru
ORCID iD: 0000-0002-1405-3723

Cancer Research Institute

Russian Federation, 5 Kooperativny Lаne, Tomsk 634009

I. K. Fedorova

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: trremar@mail.ru
ORCID iD: 0000-0002-7540-8532

Cancer Research Institute

Russian Federation, 5 Kooperativny Lаne, Tomsk 634009

R. S. Vorobev

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: trremar@mail.ru
ORCID iD: 0000-0002-5705-8479

Cancer Research Institute

Russian Federation, 5 Kooperativny Lаne, Tomsk 634009

D. E. Kulbakin

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: trremar@mail.ru
ORCID iD: 0000-0003-3089-5047

Cancer Research Institute

Russian Federation, 5 Kooperativny Lаne, Tomsk 634009

E. L. Choinzonov

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: trremar@mail.ru
ORCID iD: 0000-0002-3651-0665

Cancer Research Institute

Russian Federation, 5 Kooperativny Lаne, Tomsk 634009

E. V. Denisov

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: trremar@mail.ru
ORCID iD: 0000-0003-2923-9755

Cancer Research Institute

Russian Federation, 5 Kooperativny Lаne, Tomsk 634009

References

  1. Lenoci D., Moresco E., Cavalieri S. et al. Oral cancer in young adults: incidence, risk factors, prognosis, and molecular biomarkers. Front Oncol 2024;20;14:1452909. doi: 10.3389/fonc.2024.1452909
  2. Da Silva Souto A.C., da Silva B.N.M., Heimlich F.V. et al. Epidemiological landscape of tongue cancer in younger patients in a National Cancer Center in Brazil. Sci Rep 2024;14(1);30573. doi: 10.1038/s41598-024-83470-9
  3. Kolegova E.S., Patysheva M.R., Larionova I.V. et al. Early-onset oral cancer as a clinical entity: aetiology and pathogenesis. Int J Oral Maxillofac Surg 2022;51(12):1497–509. doi: 10.1016/j.ijom.2022.04.005
  4. Hong X., Quimby A.E., Mavedatnia D. et al. Oral cavity squamous cell carcinoma in young patients: a multi-institutional study of the Canadian Head & Neck Collaborative Research Initiative. J Otolaryngol Head Neck Surg 2025;54:19160216251351562. doi: 10.1177/19160216251351562
  5. Prostakishina E.A., Dampilova T.D., Kononova L.A. et al. The molecular landscape of oral cancer in young patients. Genetika = Russian Journal of Genetics 2023;59(11):1290–302. doi: 10.31857/S0016675823110103
  6. Patysheva M.R., Kolegova E.S., Khozyainova A.A. et al. Revealing molecular mechanisms of early-onset tongue cancer by spatial transcriptomics. Sci Rep 2024;14:26255. doi: 10.1038/s41598-024-76044-2
  7. Kolegova E.S., Korobeinikova A.A., Vorobev R.S. et al. Genetic alterations of oral cancer associated with progression in young adult. Genetika = Russian Journal of Genetics 2025;61(5):67–77. (In Russ.).doi: 10.31857/S0016675825050064
  8. Liang L.Y., Geoghegan N.D., Mlodzianoski M. et al. Co-clustering of EphB6 and ephrinB1 in trans restrains cancer cell invasion. Commun Biol 2024;7(1):461. doi: 10.1038/s42003-024-06118-4
  9. Strozen T.G., Sharpe J.C., Harris E.D. et al. The EphB6 receptor: kinase-dead but very much alive. Int J Mol Sci 2021;22(15):8211. doi: 10.3390/ijms22158211
  10. Naito Y., Yoshimura J., Morishita S., Ui-Tei K. siDirect 2.0: updated software for designing functional siRNA with reduced seed-dependent off-target effect. Available at: https://sidirect2.rnai.jp/doc
  11. National Center for Biotechnology Information. NCBI resource coordinator. Available at: https://www.ncbi.nlm.nih.gov/.
  12. InvivoGen. siRNA Wizard: Online Tool to Choose and Design short hairpin RNAs. Available at: https://www.invivogen.com/sirnawizard/
  13. Shi J., Lyu C. The role of eph/ephrin-driven actomyosin contractility in promoting cell segregation and boundary formation. Int J Mol Sci 2026;27(7):3250. doi: 10.3390/ijms27073250
  14. Poliakov A., Cotrina M., Wilkinson D.G. Diverse roles of eph receptors and ephrins in the regulation of cell migration and tissue assembly. Dev Cell 2004;7(4):465–80. doi: 10.1016/j.devcel.2004.09.006
  15. Darling T.K., Lamb T.J. Emerging roles for eph receptors and ephrin ligands in immunity. Front Immunol 2019;10:1473. doi: 10.3389/fimmu.2019.01473
  16. Pasquale E.B. Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer 2010;10(3):165–80. doi: 10.1038/nrc2806
  17. Cho H.J., Hwang Y.S., Yoon J. et al. EphrinB1 promotes cancer cell migration and invasion through the interaction with RhoGDI1. Oncogene 2018;37(7):861–72. doi: 10.1038/onc.2017.386

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2026 ABV-Press

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-57560 от  08.04.2014.