Department of Biological Sciences, Federal University of São Paulo, Diadema, São Paulo, Brazil.
J Leukoc Biol. 2013 Sep;94(3):503-12. doi: 10.1189/jlb.0113057. Epub 2013 Jun 25.
The human FMNL1 is expressed predominantly in hematopoietic cells and has been described previously as overexpressed in hematopoietic malignancies. However, it is not known whether FMNL1 contributes to leukemogenesis. Here, we investigate the FMNL1 function using two different human leukemia models: Namalwa and K562 cell lines. FMNL1 depletion reduced cell proliferation and colony formation in both leukemic cell types, as well as a decrease in the tumor growth of FMNL1-depleted Namalwa cell xenografts. In addition, there was a decrease in migration and in TEM in FMNL1-depleted Namalwa cells. FMNL1 endogenously associates with Rac1, and FMNL1 silencing resulted in an increased Rac1 activity. The reduced migration observed in FMNL1-depleted cells was restored by inhibiting Rac activity. Our results indicate that FMNL1 stimulates leukemia cell proliferation as well as migration. This suggests that FMNL1 contributes to leukemogenesis and could act in part through Rac1 regulation.
人源 FMNL1 主要在造血细胞中表达，先前已被描述为在造血恶性肿瘤中过度表达。然而，目前尚不清楚 FMNL1 是否有助于白血病的发生。在这里，我们使用两种不同的人类白血病模型（Namalwa 和 K562 细胞系）来研究 FMNL1 的功能。FMNL1 耗竭减少了两种白血病细胞类型的细胞增殖和集落形成，以及 FMNL1 耗竭的 Namalwa 细胞异种移植瘤的肿瘤生长减少。此外，FMNL1 耗竭的 Namalwa 细胞的迁移和 TEM 减少。FMNL1 与 Rac1 内源性结合，FMNL1 沉默导致 Rac1 活性增加。抑制 Rac 活性可恢复在 FMNL1 耗竭细胞中观察到的迁移减少。我们的结果表明，FMNL1 刺激白血病细胞增殖和迁移。这表明 FMNL1 有助于白血病的发生，并可能部分通过 Rac1 调节起作用。
