T细胞急性淋巴细胞白血病(T-ALL)是一种侵袭性的血液恶性肿瘤。它进展迅速，如果不接受治疗，几个月内可能会致命。尽管目前的临床治疗存在限制，但迫切需要新的靶向治疗方法。为了探索潜在的靶向治疗方法，必须揭示T-ALL转移的分子遗传机制。然而，介导T-ALL转移的基因和机制大部分仍未知。最近对T-ALL生物学的认识揭示出了几种可以分为几个可靶向的信号通路的基因。Wnt/β-连环蛋白信号通路是最重要的通路之一。我们的研究调查了TCF1和LEF1在Wnt信号通路介导的细胞生长和迁移中的作用。我们发现，TCF1和LEF1的缺失虽然微弱地抑制了T-ALL细胞增殖，但明显地损伤了细胞迁移。T-ALL的转移与细胞迁移和侵袭相关。我们的研究结果表明，通过Wnt依赖的趋化因子和细胞因子诱导的炎症和cadherin信号通路，TCF1和LEF1调节了T-ALL细胞的迁移。通过转录调控这些通路相关的基因，TCF1和LEF1抑制了细胞黏附并促进了细胞的迁移和侵袭。© 2023 The Authors.

T-cell acute lymphoblastic leukemia (T-ALL) is a type of aggressive hematologic malignancy. It progresses quickly and it is likely to be fatal within a few months without treatment. Despite the limitations of current clinical therapies, there is an urgent need for novel and targeted therapies. To explore potential targeted therapies, molecular genetic mechanisms of T-ALL metastasis must be uncovered. However, the genes and mechanisms that mediate T-ALL metastasis are largely unknown. Recent insights into T-ALL biology have identified several genes that can be grouped into several targetable signaling pathways. The Wnt/β-catenin signaling pathway is one of the most important pathways. Our work investigated the functions of TCF1 and LEF1 in cell growth and migration mediated by the Wnt signaling pathway. We found that TCF1 and LEF1 knockdown weakly repressed T-ALL cell proliferation but distinctly impaired cell migration. T-ALL metastasis is dependent on cell migration and invasion. Our results displayed that TCF1 and LEF1 regulated T-ALL cell migration by the Wnt-dependent chemokine and cytokine-induced inflammation and cadherin signaling pathways. By transcriptionally regulating these pathways-associated genes, TCF1 and LEF1 inhibited cell adhesion and promoted cell migration and invasion.© 2023 The Authors.