The intracellular negative regulator genes of the Wnt signaling in imatinib treatment

The intracellular negative regulator genes of the Wnt signaling in imatinib treatment

Aim: Tyrosine kinase inhibitors are a targeted and successful treatment modalities in the treatment of Chronic Myeloid Leukemia (CML). Imatinib mesylate is the most common of these inhibitors, but resistance reactions limit its use. It is believed that regulators in the Wnt signaling pathway play an important role in the treatment of CML. The aim of this study is to investigate possible expression changes of intracellular negative regulator genes after imatinib mesylate treatment in chronic myeloid leukemia cell line. Materials and Methods: Total RNA isolation was performed from K562 cells treated with Imatinib mesylate for 24 hours at 0.5 µM concentration and control native K562 cells. Following cDNA synthesis, expression changes of eight intracellular negative regulator genes were analyzed by Real-Time PCR. Results: When the results were evaluated, it was determined that the expression of 5 genes increased and the expression of 3 genes decreased in K562 cells treated with imatinib. Conclusion: When we suppressed Bcr-Abl with Imatinib in K562 cells, it was observed that there were changes in the expression levels of the intracellular negative regulator genes of the Wnt signaling pathway. These changes are important in defining new targets in CML treatment. To understand the roles of these negative regulators, it is important to conduct detailed research to develop new strategies for CML treatment.

___

  • 1. Albano F, Zagaria A, Anelli L, et al. Gene expression profiling of chronic myeloid leukemia with variant t(9;22) reveals a different signature from cases with classic translocation. Mol Cancer 2013;12:1-5.
  • 2. Bernardo PS, Lemos LGT, Moraes GN, et al. Unraveling survivin expression in chronic myeloid leukemia. Molecular interactions and clinical implications. Blood Reviews 2020;43:100671.
  • 3. Pehlivan M, Caliskan C, Yuce Z, et al. Forced expression of Wnt antagonists sFRP1 and WIF1 sensitizes chronic myeloid leukemia cells to tyrosine kinase inhibitors. Tumour Biol 2017;39:1-9.
  • 4. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring. Am J Hematol 2020; 95:691-709.
  • 5. Casolari DA, Melo JV. Chronic myeloid leukaemia. Chromosom Translocat Genome Rearrange Cancer 2015; 385:107-38.
  • 6. Iqbal N, Iqbal N. Imatinib: a breakthrough of targeted therapy in cancer. Chemother Res Pract 2014;2014:1- 9.
  • 7. Zhao C, Blum J, Chen A, et al. Loss of β-catenin impairs the renewal of normal and cml stem cells in vivo. Cancer Cell 2007;12:528-41.
  • 8. Luce Coluccia AM, Vacca A, Duñach M, et al. BcrAbl stabilizes β-catenin in chronic myeloid leukemia through its tyrosine phosphorylation. The EMBO J 2007;26:1456-66.
  • 9. Slattery ML, Mullany LE, Sakoda LC, et al. Expression of Wnt-signaling pathway genes and their associations with miRNAs in colorectal cancer. Oncotarget 2017;23;9:6075-85.
  • 10. Paluszczak J, Sarbak J, Kostrzewska-Poczekaj M, et al. The negative regulators of Wnt pathwayDACH1, DKK1, and WIF1 are methylated in oral and oropharyngeal cancer and WIF1 methylation predicts shorter survival. Tumour Biol 2015;36:2855-61.
  • 11. Song Z, Wang H, Zhang S. Negative regulators of Wnt signaling in non-small cell lung cancer: theoretical basis and therapeutic potency, Biomed & Pharmacother 2019;118:1-15
  • 12. Zhang X, Lou Y, Zheng X, et al. Wnt blockers inhibit the proliferation of lung cancer stem cells. Drug Des Devel Ther 2015;28:2399-407.
  • 13. Zmijanac Partl J, Karin V, Skrtic A, et al. Negative regulators of Wnt signaling pathway SFRP1 and SFRP3 expression in preterm and term pathologic placentas. J Matern Fetal Neonatal Med 2018;31:2971-9.
  • 14. Stewart DJ. Wnt signaling pathway in non-small cell lung cancer. J Natl Cancer Inst 2014;106:1-11.
  • 15. Sercan HO, Pehlivan M, Simsek O, et al. Induction of apoptosis increases expression of non-canonical WNT genes in myeloid leukemia cell lines. Oncology Reports 2007;18:1563-9.
  • 16. Akiyama T. Wnt/β-catenin signaling. Cytokine and Growth Factor Reviews 2000;11:273-82.
  • 17. Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci USA 2006;103:2794-9.
  • 18. Hu Y, Chen Y, Douglas L, et al. beta-Catenin is essential for survival of leukemic stem cells insensitive to kinase inhibition in mice with Bcr-Abl-induced chronic myeloid leukemia. Leukemia 2009;23:109-16.
  • 19. Corrêa S, Binato R, Du Rocher B, et al. Wnt/β-catenin pathway regulates ABCB1 transcription in chronic myeloid leukemia. BMC Cancer 2011;23:303.
  • 20. van Andel, H, Kocemba KA, Spaargaren M, et al. Aberrant Wnt signaling in multiple myeloma: molecular mechanisms and targeting options. Leukemia 2019;33:1063-75.
  • 21. Jiang S, Zhang M, Sun J, et al. Casein kinase 1α: biological mechanisms and theranostic potential. Cell Commun Signal 2018;16:1-24.
  • 22. Järås M, Miller PG, Chu LP, et al. Csnk1a1 inhibition has p53-dependent therapeutic efficacy in acute myeloid leukemia. J Exp Med 2014;211:605-12.
  • 23. Shi Q, Liu H, Han P, et al. Genetic Variants in WNT2B and BTRC Predict Melanoma Survival. J Invest Dermatol 2017;137:1749-56.
  • 24. Yumimoto K, Yamauchi Y, Nakayama I. F-Box Proteins and Cancer. Cancers 2020;12:1249-76.
  • 25. Wolter M, Scharwächter C, Reifenberger J, et al. Absence of detectable alterations in the putative tumor suppressor gene BTRC in cerebellar medulloblastomas and cutaneous basal cell carcinomas. Acta Neuropathol 2003;106:287-90.
  • 26. Guo M, Zhang X, Wang G, et al. miR-603 promotes glioma cell growth via Wnt/β-catenin pathway by inhibiting WIF1 and CTNNBIP1. Cancer Lett 2015;360:76-86.
  • 27. Chang JM, Tsai AC, Huang WR, et al. The Alteration of CTNNBIP1 in Lung Cancer. Int J Mol Sci 2019;20:5684- 98.
  • 28. Fang M, Li J, Blauwkamp T, et al. C-terminalbinding protein directly activates and represses Wnt transcriptional targets in Drosophila. EMBO J 2006;25:2735-45.
  • 29. Blevins MA, Huang M, Zhao R. The Role of CtBP1 in Oncogenic Processes and Its Potential as a Therapeutic Target. Mol Cancer Ther 2017;16:981-90.
  • 30. Hamada F, Bienz M. The APC tumor suppressor binds to C-terminal binding protein to divert nuclear betacatenin from TCF. Dev Cell 2004;7:677-85.
  • 31. Dcona MM, Morris BL, Ellis KC, et al. CtBP- an emerging oncogene and novel small molecule drug target: Advances in the understanding of its oncogenic action and identification of therapeutic inhibitors. Cancer Biol Ther 2017;18:379-91.
  • 32. Chan DW, Chan CY, Yam JW, Ching YP, Ng IO. Prickle-1 negatively regulates Wnt/beta-catenin pathway by promoting Dishevelled ubiquitination/degradation in liver cancer. Gastroenterology. 2006;131:1218-27.
  • 33. Kaucká M, Plevová K, Pavlová Š, et al. The planar cell polarity pathway drives pathogenesis of chronic lymphocytic leukemia by the regulation of b-lymphocyte migration. Cancer Res 2013;73:1491- 501.
  • 34. Zhou JD, Yao DM, Han L, et al. Low NKD1 expression predicts adverse prognosis in cytogenetically normal acute myeloid leukemia. Tumour Biol 2017;39:1-8.
  • 35. Mukherjee S, Chaturvedi P, Rankin SA, et al. Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endoderm gene regulatory network. Elife 2020;9:1-26
  • 36. Li L, Yang WT, Zheng PS, et al. SOX17 restrains proliferation and tumor formation by down-regulating activity of the Wnt/β-catenin signaling pathway via trans-suppressing β-catenin in cervical cancer. Cell Death Dis 2018;9:1-16.
Annals of Medical Research-Cover
  • Yayın Aralığı: Aylık
  • Yayıncı: İnönü Üniversitesi Tıp Fakültesi
Sayıdaki Diğer Makaleler

Cognitive home environment of infants, toddlers and preschoolers: A study from a hospital setting

Sinem Kortay Canaloglu, Derya Gumus Dogan, Mehmet Akif Buyukavci, Feyzullah Necati Arslan

Bilateral endometriotic cyst with extremely high Ca-125 and Ca-19-9 levels caused by chronic leakage of cyst fluid: A case report

Kadir Cetinkaya, Serkan Kahyaoglu, Belma Gozde Ozdemir

Effects of ApaI, FokI, and BsmI gene polymorphisms of the vitamin D receptor on serum vitamin D level in Turkish MS patients with different types and severities of the disease

Asli Bolayir, Malik Ejder Yildirim, Tugba Turker Cetinel, Seyda Figul Gokce

Prognostic factors and classification of pathological single and multiple N1 in non-small cell lung cancer patients

Ali Cevat Kutluk, Muzaffer Metin, Cemal Aker, Volkan Erdogu, Atilla Pekcolaklar, Ozkan Saydam, Deniz Sansar, Selin Onay

Comparison of the results between monocanalicular and bicanalicular silicone tube intubation in children with congenital nasolacrimal duct obstruction

Soner Demirel, Ulku Demir

Cardiovascular disease in type 2 diabetes mellitus: Relationship between microalbuminuria and cardiovascular risk factors

Mehmet Sozen, Damla Koksalan, Kubra Solmaz, Esma Altunoglu

The intracellular negative regulator genes of the Wnt signaling in imatinib treatment

Hakki Ogun Sercan, Melek Pehlivan, Burcu Cerci

Factors effecting the development of sentinel lymph node metastasis in clinical early-stage breast cancers (cT1-2N0): Clinical significance of primary tumor – skin distance

Azmi Lale, Erhan Aygen, Hatice Nur Lale, Levent Zirek, Merve Zirek, Ali Cihan Yildirir

Evaluation of demographic data and laboratory of children receiving subcutaneous venom immunotherapy

Erdem Topal, Fatih Kaplan

Levels of interleukin-8 and catalase have correlations with zinc in healthy adults: Implications for inflammatory conditions

Ganiyu Olatunbosun Arinola, Fabian Victory Edem