Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Anticancer Effects of Fibronectin Leucine Rich Transmembrane Protein 3 as a Novel Therapeutic Molecule in Lung Cancer and Lung Cancer-derived Stem Cell

  • Joong-Won Baek (Department of Biomedical Laboratory Science, Konyang University) ;
  • Pyung-Hwan Kim (Department of Biomedical Laboratory Science, Konyang University)
  • Received : 2023.11.15
  • Accepted : 2023.12.07
  • Published : 2023.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Lung cancer is one of the cancers with high mortality and incidence rates worldwide. Although, various anticancer research efforts are underway to completely treat cancer, the challenge against it remains in the inability to eliminate cancer stem cells (CSCs), leading to difficulties in curing the cancer and resulting in recurrence. As a result, there is a growing interest in the discovery of new biomarkers and therapeutic molecules that can simultaneously target both cancer cells and CSCs. From this point of view, we focused on fibronectin leucine rich transmembrane protein 3 (FLRT3), one of the genes known to be present in human lung cells and the discovery from our previous cancer proteomic analysis study. This study aimed to evaluate the potential of FLRT3 as a specific therapeutic biomarker for lung cancer and Lung Cancer-derived-Stem Cells (LCSC). Also, to estimate the biological function of FLRT3 in cancer and LCSC, short hairpin RNA (shRNA) was generated and showed the ability of the decreased-cell migration and cell proliferation of lung cancer through ERK signaling pathway when FLRT3 was knock-downed. In conclusion, our study is the first to report that FLRT3 has the potential as therapeutic biomarker for the treatment of lung cancer and LCSC.

Keywords

Acknowledgement

Following are results of a study on the "Leaders in Industry-university Cooperation 3.0" Project and Basic Science Research Program (2020R1F1A1053663) supported by the Ministry of Education and National Research Foundation of Korea.

References

  1. Barta JA, Powell CA, Wisnivesky JP. Global epidemiology of lung cancer. Annals of Global Health. 2019. 85.
  2. Calabro L, Rossi G, Covre A, Morra A, Maio M. COVID and lung cancer. Current Oncology Reports. 2021. 23: 1-10. https://doi.org/10.1007/s11912-021-01125-8
  3. Chen X, Koh E, Yoder M, Gumbiner BM. A protocadherin-cadherin-FLRT3 complex controls cell adhesion and morphogenesis. PloS One. 2009. 4: e8411.
  4. Cojoc M, Mabert K, Muders MH, Dubrovska A. A role for cancer stem cells in therapy resistance: Cellular and molecular mechanisms. Paper presented at the Seminars in Cancer Biology. 2015. 31: 16-27. https://doi.org/10.1016/j.semcancer.2014.06.004
  5. Degirmenci U, Wang M, Hu J. Targeting aberrant RAS/RAF/MEK/ERK signaling for cancer therapy. Cells. 2020. 9: 198.
  6. Eramo A, Haas TL, De Maria R. Lung cancer stem cells: Tools and targets to fight lung cancer. Oncogene. 2010. 29: 4625-4635. https://doi.org/10.1038/onc.2010.207
  7. Guo X, Song C, Fang L, Li M, Yue L, Sun Q. FLRT2 functions as tumor suppressor gene inactivated by promoter methylation in colorectal cancer. Journal of Cancer. 2020. 11: 7329.
  8. Hardavella G, George R, Sethi T. Lung cancer stem cells-characteristics, phenotype. Translational Lung Cancer Research. 2016. 5: 272.
  9. Huang J, Ngai CH, Deng Y, Tin MS, Lok V, Zhang L, Yuan J, Xu W, Zheng Z-J, Wong MC. Cancer incidence and mortality in asian countries: A trend analysis. Cancer Control. 2022. 29: 10732748221095955.
  10. Jung K, Won Y, Kong H, Lee ES. Cancer statistics in korea: Incidence, mortality, survival, and prevalence in 2016. Cancer Research and Treatment: Official Journal of Korean Cancer Association. 2019. 51: 417-430. https://doi.org/10.4143/crt.2019.138
  11. Koh E, Kim K, Park H, Kim J, Kim P. Active targeting of versatile nanocomplex using the novel biomarker of breast cancer stem cells. International Journal of Molecular Sciences. 2022. 24: 685.
  12. Krakhmal NV, Zavyalova MV, Denisov EV, Vtorushin SV, Perelmuter VM. Cancer invasion: Patterns and mechanisms. Acta Naturae. 2015. 7: 17-28. https://doi.org/10.32607/20758251-2015-7-2-17-28
  13. Lacy SE, Bonnemann CG, Buzney EA, Kunkel LM. Identification of FLRT1, FLRT2, and FLRT3: A novel family of transmembrane leucine-rich repeat proteins. Genomics. 1999. 62: 417-426. https://doi.org/10.1006/geno.1999.6033
  14. Lundin A, Driscoll B. Lung cancer stem cells: Progress and prospects. Cancer Letters. 2013. 338: 89-93. https://doi.org/10.1016/j.canlet.2012.08.014
  15. Najafi M, Majidpoor J, Toolee H, Mortezaee K. The current knowledge concerning solid cancer and therapy. Journal of Biochemical and Molecular Toxicology. 2021. 35: e22900.
  16. Ren M, Xu W, Xu T. Salidroside represses proliferation, migration and invasion of human lung cancer cells through AKT and MEK/ERK signal pathway. Artificial Cells, Nanomedicine, and Biotechnology. 2019. 47: 1014-1021. https://doi.org/10.1080/21691401.2019.1584566
  17. Schiliro C, Firestein BL. Mechanisms of metabolic reprogramming in cancer cells supporting enhanced growth and proliferation. Cells. 2021. 10: 1056.
  18. Sharma P, Mehta M, Dhanjal DS, Kaur S, Gupta G, Singh H, Thangavelu L, Rajeshkumar S, Tambuwala M, Bakshi HA. Emerging trends in the novel drug delivery approaches for the treatment of lung cancer. Chemico-Biological Interactions. 2019. 309: 108720.
  19. Shiga K, Hara M, Nagasaki T, Sato T, Takahashi H, Takeyama H. Cancer-associated fibroblasts: Their characteristics and their roles in tumor growth. Cancers. 2015. 7: 2443-2458. https://doi.org/10.3390/cancers7040902
  20. Suresh R, Ali S, Ahmad A, Philip PA, Sarkar FH. The role of cancer stem cells in recurrent and drug-resistant lung cancer. Lung Cancer and Personalized Medicine: Novel Therapies and Clinical Management. 2016. 57-74.
  21. Ullah R, Yin Q, Snell AH, Wan L. RAF-MEK-ERK pathway in cancer evolution and treatment. Paper presented at the Seminars in Cancer Biology. 2022. 85: 123-154. https://doi.org/10.1016/j.semcancer.2021.05.010