Microscopic indications of malignancy and hallmark molecules of cancer are pivotal to determining cancer patient prognosis and subsequent medical intervention. Here, we found that compared to apical expression of Cdc42, which indicated that basal expression of Cdc42 occurred at the migrating cell front, glandular basal expression of Cdc42 (cell division cycle 42) in tissues indicated poorer prognoses for colorectal cancer (CRC) patients. The current study shows that activated Cdc42 was rapidly recruited to the migrating CRC cell front after VEGF stimulation through engagement of membrane-anchored neuropilin-1 (NRP1). When VEGF signalling was blocked with NRP1 knockdown or ATWLPPR (A7R, antagonist of VEGF/NRP1 interaction), Cdc42 activation and relocation to the cell front was attenuated, and filopodia and invadopodia formation was inhibited. The VEGF/NRP1 axis regulates directional migration, invasion, and metastasis through Cdc42 activation and relocation resulting from actin filament polymerisation of the extensions of membrane protrusions. Collectively, the immuno-micromorphological pattern of subcellular Cdc42 at the cell front indicated aggressive behaviours and predicted poor prognosis in CRC patients. Disruption of the intra- and extracellular interactions of the VEGF/NRP1 axis or Cdc42 relocation could be performed in clinical practice because it might inhibit cancer cell motility and metastasis.

恶性肿瘤的微观迹象和癌症的标志分子对于确定癌症患者的预后和随后的医疗干预至关重要。在这里，我们发现，与 Cdc42 的顶端表达（表明 Cdc42 的基础表达发生在迁移细胞前端）相比，组织中 Cdc42（细胞分裂周期 42）的腺体基础表达表明结直肠癌（CRC）患者的预后较差。目前的研究表明，在 VEGF 刺激后，通过膜锚定神经毡蛋白-1 (NRP1) 的参与，激活的 Cdc42 被快速招募到迁移的 CRC 细胞前沿。当用 NRP1 敲低或 ATWLPPR（A7R，VEGF/NRP1 相互作用的拮抗剂）阻断 VEGF 信号传导时，Cdc42 激活和向细胞前端的重新定位减弱，丝状伪足和侵袭伪足的形成受到抑制。VEGF/NRP1 轴通过膜突起延伸的肌动蛋白丝聚合引起的 Cdc42 激活和重新定位来调节定向迁移、侵袭和转移。总的来说，细胞前端的亚细胞 Cdc42 的免疫微形态模式表明了 CRC 患者的攻击行为并预测不良预后。破坏 VEGF/NRP1 轴的细胞内和细胞外相互作用或 Cdc42 重新定位可以在临床实践中进行，因为它可能会抑制癌细胞的运动和转移。