PRICKLE1 promotes gastric cancer metastasis by activating mTOR signaling.

Lymph node metastasis confers an unfavorable prognosis in gastric cancer (GC). Transcriptomic sequencing has been used to explore the molecular changes in metastatic cancers, but the changes of expression profiling of metastatic GC in lymph nodes remain largely unknown. To identify the potential driver genes, we performed whole transcriptomic sequencing (RNA-seq) on five pairs of gastric adenocarcinoma specimens with metastatic lymph nodes confirmed by pathology. We identified six genes associated with lymph node metastasis and predicted poor prognosis in GC patients. Finally, we focused on PRICKLE1, a cell polarity protein, which dramatically upregulated in several GC cell lines from metastatic lesions compared with those from the primary tumor. Loss and gain of function assay in vitro showed that the migration and invasion capability of GC cells were limited by downregulating and upregulating PRICKLE1 expression. Mechanically, we found PRICKLE1 might modulate tumor metastasis through mTOR signaling pathway. Inhibition of mTOR significantly reduced GC cell migration and invasion in vitro. In summary, we identified and validated PRICKLE1 as a novel gene involved in GC metastasis. This study provided a valuable insight into the mechanisms of GC metastasis and developed a potential therapeutic target to prevent GC cell dissemination. AJTR