膀胱癌（BCa）是一种全球致命的癌症形式，与不良预后有关。识别生长和转移的新型驱动因素具有治疗该疾病的潜力。内质网和高尔基之间的运输平衡以及由高尔基介导的基质金属蛋白酶（MMPs）的分泌被报道与肿瘤进展密切相关。然而，到目前为止，机械研究仍然有限。在这里，我们识别了KDELR2作为一种潜在的风险因素，在BCa患者中具有预后价值，特别是那些携带KDELR2扩增的患者。此外，我们发现，在生物信息学分析和功能研究基础上，KDELR2是BCa细胞增殖和肿瘤生成性的调节因素。在机械上，我们揭示了KDELR2可以调节KIF20A的表达，从而刺激MMP2、MMP9和MKI67的表达。在功能上，KDELR2和KIF20A的过表达显著促进了体外增殖、迁移和侵袭，并在体内增强了肿瘤生长，而KDELR2和KIF20A的沉默产生了相反的效应。KDELR2过度表达还在体内增强了淋巴结转移。综上所述，我们的发现阐明了KDELR2-KIF20A轴在增加高尔基介导的MMPs分泌以推动BCa肿瘤进展方面迄今尚未探索的机制。©2022。作者（们）。

Bladder cancer (BCa) is a fatal form of cancer worldwide associated with a poor prognosis. Identifying novel drivers of growth and metastasis hold therapeutic potential for the disease. Transport homeostasis between the endoplasmic reticulum and Golgi and the secretion of matrix metalloproteinases (MMPs) mediated by Golgi have been reported to be closely associated with tumor progression. However, to date, mechanistic studies remain limited.Here, we identified KDELR2 as a potential risk factor with prognostic value in patients with BCa, especially those harbouring the KDELR2 amplification. In addition, we found that KDELR2 is a regulator of BCa cell proliferation and tumorigenicity based on bioinformatic analysis with functional studies. Mechanistically, we revealed that KDELR2 could regulate the expression of KIF20A, thus stimulating the expression of MMP2, MMP9 and MKI67. Functionally, the overexpression of KDELR2 and KIF20A markedly promoted proliferation, migration, and invasion in vitro and enhanced tumor growth in vivo, while knockdown of KDELR2 and KIF20A exerted the opposite effects. And the overexpression of KDELR2 also enhanced lymph node metastasis in vivo.Collectively, our findings clarified a hitherto unexplored mechanism of KDELR2-KIF20A axis in increasing Golgi-mediated secretion of MMPs to drive tumor progression in BCa.© 2022. The Author(s).