Through activation of the ERK pathway, nicotine, in both normal MCF‐10A and low‐malignant breast cancer cells (MCF7), promotes increased motility and invasiveness. Melatonin antagonizes both these effects by inhibiting almost completely ERK phosphorylation. As melatonin has no effect on nonstimulated cells, it is likely that melatonin can counteract ERK activation only downstream of nicotine‐induced activation. This finding suggests that melatonin hampers ERK phosphorylation presumably by targeting a still unknown intermediate factor that connects nicotine stimulation to ERK phosphorylation. Furthermore, downstream of ERK activation, melatonin significantly reduces fascin and calpain activation while restoring normal vinculin levels. Melatonin also counteracts nicotine effects by reshaping the overall cytoskeleton architecture and abolishing invasive membrane protrusion. In addition, melatonin decreases nicotine‐dependent ROCK1/ROCK2 activation, thus further inhibiting cell contractility and motility. Melatonin actions are most likely attributable to ERK inhibition, although melatonin could display other ERK‐independent effects, namely through a direct modulation of additional molecular and structural factors, including coronin, cofilin, and cytoskeleton components.

中文翻译：

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褪黑激素通过抑制ERK磷酸化消除了尼古丁诱导的MCF7癌细胞运动性和侵袭性的增加。

通过激活ERK途径，正常MCF-10A和低恶性乳腺癌细胞（MCF7）中的尼古丁可促进运动性和侵袭性。褪黑素通过几乎完全抑制ERK磷酸化来拮抗这两种作用。由于褪黑激素对未刺激的细胞没有影响，因此褪黑激素可能只能在尼古丁诱导的激活的下游抵消ERK激活。这一发现表明，褪黑素大概是通过靶向仍然未知的将尼古丁刺激与ERK磷酸化联系起来的中间因子而阻碍ERK磷酸化。此外，在ERK激活的下游，褪黑激素显着​​降低了肌钙蛋白和钙蛋白酶的激活，同时又恢复了正常的纽蛋白水平。褪黑激素还可以通过重塑整体细胞骨架结构和消除侵入性膜突出来抵消尼古丁的作用。此外，褪黑激素降低了尼古丁依赖性的ROCK1 / ROCK2活化，从而进一步抑制了细胞的收缩性和运动性。褪黑激素的作用很可能归因于ERK的抑制，尽管褪黑激素可能表现出其他与ERK无关的作用，即通过直接调节其他分子和结构因素，包括冠蛋白，cofilin和细胞骨架成分。