Metastatic progression combined with non-responsiveness towards systemic therapy often shapes the course of disease for cancer patients and commonly determines its lethal outcome. The complex molecular events that promote metastasis are a combination of both, the acquired pro-metastatic properties of cancer cells and a metastasis-permissive or -supportive tumor micro-environment (TME). Yet, dissemination is a challenging process for cancer cells that requires a series of events to enable cancer cell survival and growth. Metastatic cancer cells have to initially detach themselves from primary tumors, overcome the challenges of their intravasal journey and colonize distant sites that are suited for their metastases. The implicated obstacles including anoikis and immune surveillance, can be overcome by intricate intra- and extracellular signaling pathways, which we will summarize and discuss in this review. Further, emerging modulators of metastasis, like the immune-microenvironment, microbiome, sublethal cell death engagement, or the nervous system will be integrated into the existing working model of metastasis.

转移进展加上对全身治疗无反应通常决定癌症患者的病程，并通常决定其致命结果。促进转移的复杂分子事件是癌细胞获得的促转移特性和允许转移或支持转移的肿瘤微环境（TME）的组合。然而，扩散对于癌细胞来说是一个具有挑战性的过程，需要一系列事件才能使癌细胞存活和生长。转移性癌细胞必须首先从原发性肿瘤中分离出来，克服其血管内旅程的挑战，并定植到适合其转移的远处部位。包括失巢凋亡和免疫监视在内的相关障碍可以通过复杂的细胞内和细胞外信号通路来克服，我们将在这篇综述中总结和讨论。此外，新兴的转移调节剂，如免疫微环境、微生物组、亚致死细胞死亡参与或神经系统，将被整合到现有的转移工作模型中。