Condensation of the Golgi Apparatus Activates YAP1 to Promote Gastric Cancer Progression.

UNLABELLED: Alterations in the structure of the Golgi apparatus play a pivotal role in cancer progression and invasion. A better understanding of how Golgi morphology regulates the metastatic potential of cancer cells could help identify potential treatment strategies. In this study, we investigated how specific structural variations in the Golgi, particularly fragmentation and condensation, influence the malignancy of gastric cancer using human cell lines, xenograft mouse models, and human patient tissue samples. Gastric cancer cells with condensed Golgi structures exhibited increased proliferation and migration. Mechanistic analyses indicated that Golgi condensation-associated malignancy was driven by enhanced formation of Golgi-derived microtubules, elevated vesicular trafficking, and augmented nuclear translocation of YAP1, a key transcriptional regulator of cell proliferation and tumorigenesis. Importantly, treatment with an agent that induces Golgi fragmentation significantly suppressed tumor growth in a xenograft mouse model. Furthermore, signet-ring cell carcinoma, an aggressive subtype of diffuse gastric cancer, exhibited a stronger inverse correlation between YAP1 activation and the Golgi area than both intestinal-type and non-signet ring cell carcinoma. These findings underscore the critical role of Golgi apparatus dynamics in oncogenic signaling pathways and reveal therapeutic targets in gastric cancer.

SIGNIFICANCE: Golgi condensation facilitates YAP1-mediated oncogenic progression in gastric cancer, highlighting Golgi structural modulation as a promising therapeutic strategy to inhibit malignant signaling and cellular dissemination.