Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, Lund, Sweden.
Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Sci Rep. 2017 Oct 23;7(1):13734. doi: 10.1038/s41598-017-14033-4.
The non-receptor tyrosine kinase LCK belongs to the SRC family of kinases. SRC family kinases are proto-oncogenes that have long been known to play key roles in cell proliferation, motility, morphology and survival. Here we show that LCK regulates the function of the type III receptor tyrosine kinase FLT3 in murine pro-B cells. We observed that expression of LCK significantly enhances the colony forming capacity of the constitutively active FLT3 mutant FLT3-ITD (internal tandem duplication). Furthermore, cells expressing LCK developed tumor earlier compared to cells transfected with empty control vector. Staining of the tissues from mouse xenografts showed higher Ki67 staining in cells expressing LCK suggesting that expression of LCK enhances the FLT3-ITD-mediated proliferative capacity. LCK expression did not affect either FLT3-WT or FLT3-ITD -induced AKT, ERK1/2 or p38 phosphorylation. However, LCK expression significantly enhanced FLT3-ITD-mediated STAT5 phosphorylation. Taken together, our data suggest that LCK cooperates with oncogenic FLT3-ITD in cellular transformation.
非受体酪氨酸激酶 LCK 属于 SRC 家族激酶。SRC 家族激酶是原癌基因，长期以来一直被认为在细胞增殖、运动性、形态和存活中发挥关键作用。在这里，我们表明 LCK 调节鼠前 B 细胞中 III 型受体酪氨酸激酶 FLT3 的功能。我们观察到 LCK 的表达显著增强了组成性激活的 FLT3 突变体 FLT3-ITD（内部串联重复）的集落形成能力。此外，与转染空载体的细胞相比，表达 LCK 的细胞更早地形成肿瘤。对来自小鼠异种移植物的组织进行染色显示，表达 LCK 的细胞中 Ki67 染色更高，这表明 LCK 的表达增强了 FLT3-ITD 介导的增殖能力。LCK 表达不影响 FLT3-WT 或 FLT3-ITD 诱导的 AKT、ERK1/2 或 p38 磷酸化。然而，LCK 表达显著增强了 FLT3-ITD 介导的 STAT5 磷酸化。总之，我们的数据表明 LCK 与致癌性 FLT3-ITD 协同作用于细胞转化。
