Meyer Florian, Lungu Cristiana, Noll Bettina, Benz David, Fränkle Felix, Ferreira Miguel Â, Tamas Raluca, Olayioye Monilola A
University of Stuttgart, Institute of Cell Biology and Immunology, 70569 Stuttgart, Germany.
University of Stuttgart, Stuttgart Research Center Systems Biology, 70569 Stuttgart, Germany.
iScience. 2025 May 9;28(6):112618. doi: 10.1016/j.isci.2025.112618. eCollection 2025 Jun 20.
Rho GTPases are key regulators of cell motility and membrane trafficking, influencing critical processes such as epithelial-mesenchymal transition (EMT). Among them, the small GTPase RhoB plays a pivotal role, but the mechanisms underlying its regulation remain largely unclear. We have previously identified the Rho guanine nucleotide exchange factor (RhoGEF) Solo (ARHGEF40) as a regulator of endosomal RhoB in epithelial cells. Here, we find that Solo is upregulated in breast cancer cells with high EMT scores and promotes cell motility through its RhoGEF activity. Solo's ability to enhance migration is further regulated by phosphorylation at tyrosine 242, mediated by the proto-oncogene Src. By combining high-resolution imaging with photoconversion assays, we further demonstrate that Solo regulates Src trafficking dynamics, localization, and consequently signaling at focal adhesions. Together, our data identify Solo as a novel feedback regulator of Src and a key driver of the motility of breast cancer cells with mesenchymal characteristics.
Rho GTP酶是细胞运动和膜运输的关键调节因子，影响上皮-间质转化（EMT）等关键过程。其中，小GTP酶RhoB发挥着关键作用，但其调节机制仍 largely不清楚。我们之前已将Rho鸟嘌呤核苷酸交换因子（RhoGEF）Solo（ARHGEF40）鉴定为上皮细胞内体RhoB的调节因子。在此，我们发现Solo在具有高EMT评分的乳腺癌细胞中上调，并通过其RhoGEF活性促进细胞运动。原癌基因Src介导的酪氨酸242磷酸化进一步调节Solo增强迁移的能力。通过将高分辨率成像与光转化分析相结合，我们进一步证明Solo调节Src运输动力学、定位，并因此调节粘着斑处的信号传导。总之，我们的数据将Solo鉴定为Src的新型反馈调节因子以及具有间充质特征的乳腺癌细胞运动的关键驱动因子。
