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

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. 2020 Nov 27;: Authors: Zhang H, Wang Y, Yang H, Huang Z, Wang X, Feng W 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 upregulate...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research