Open Access

TCF7 knockdown inhibits the imatinib resistance of chronic myeloid leukemia K562/G01 cells by neutralizing the Wnt/β‑catenin/TCF7/ABC transporter signaling axis

  • Authors:
    • Hui Zhang
    • Yonghong Wang
    • Hao Yang
    • Zhenglan Huang
    • Xin Wang
    • Wenli Feng
  • View Affiliations

  • Published online on: November 27, 2020     https://doi.org/10.3892/or.2020.7869
  • Pages: 557-568
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Clinical resistance to ABL tyrosine kinase inhibitor (TKI) imatinib remains a critical issue in the treatment of chronic myeloid leukemia (CML). Transcription factor 7 (TCF7) is one of the main Wnt/β‑catenin signaling mediators. Previous studies have shown that TCF7 is vital for tumor initiation, and targeting TCF7 can reduce drug resistance in many types of cancer. However, the role of TCF7 in CML imatinib‑resistant cells is unclear. In the present study, we analyzed the transcriptomic data from CML clinical samples in the Gene Expression Omnibus (GEO) and performed experimental verification in the CML imatinib‑resistant cell line K562/G01. We found that the expression of TCF7 was independent of BCR‑ABL1 activity. Silencing of TCF7 downregulated the expression levels of CTNNB1, CCND1, and ABCC2, and therefore inhibited proliferation, weakened colony formation, and increased the drug sensitivity of imatinib‑resistant cells. After analyzing the transcriptomic data of four groups (Scramble, TCF7_KD, Scramble+imatinib, and TCF7_KD+imatinib) using bioinformatics, we noted that Wnt/β‑catenin and ATP‑binding cassette (ABC) transporter signaling pathways were upregulated in imatinib‑resistant cells under conventional dose of imatinib, and TCF7 knockdown could neutralize this effect. Next, using ChIP‑qPCR, we demonstrated that TCF7 was recruited to the promoter region of ABCC2 and activated gene transcription. In summary, our results highlight that the upregulation of Wnt/β‑catenin and ABC transporter signaling pathways induced by imatinib treatment of resistant cells confers imatinib resistance, and reveal that targeting TCF7 to regulate the Wnt/β‑catenin/TCF7/ABC transporter signaling axis may represent an effective strategy for overcoming imatinib resistance.
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February-2021
Volume 45 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhang H, Wang Y, Yang H, Huang Z, Wang X and Feng W: TCF7 knockdown inhibits the imatinib resistance of chronic myeloid leukemia K562/G01 cells by neutralizing the Wnt/β‑catenin/TCF7/ABC transporter signaling axis. Oncol Rep 45: 557-568, 2021.
APA
Zhang, H., Wang, Y., Yang, H., Huang, Z., Wang, X., & Feng, W. (2021). TCF7 knockdown inhibits the imatinib resistance of chronic myeloid leukemia K562/G01 cells by neutralizing the Wnt/β‑catenin/TCF7/ABC transporter signaling axis. Oncology Reports, 45, 557-568. https://doi.org/10.3892/or.2020.7869
MLA
Zhang, H., Wang, Y., Yang, H., Huang, Z., Wang, X., Feng, W."TCF7 knockdown inhibits the imatinib resistance of chronic myeloid leukemia K562/G01 cells by neutralizing the Wnt/β‑catenin/TCF7/ABC transporter signaling axis". Oncology Reports 45.2 (2021): 557-568.
Chicago
Zhang, H., Wang, Y., Yang, H., Huang, Z., Wang, X., Feng, W."TCF7 knockdown inhibits the imatinib resistance of chronic myeloid leukemia K562/G01 cells by neutralizing the Wnt/β‑catenin/TCF7/ABC transporter signaling axis". Oncology Reports 45, no. 2 (2021): 557-568. https://doi.org/10.3892/or.2020.7869