A study identifies tiRNA-Val-CAC-2 as a key regulator of pancreatic cancer metastasis. This tRNA-derived small RNA is significantly upregulated in metastatic pancreatic cancer tissues and serum samples from patients with metastasis. Overexpression of tiRNA-Val-CAC-2 promotes cancer cell migration and invasion, while its knockdown inhibits these processes. Mechanistically, tiRNA-Val-CAC-2 interacts with the RNA-binding protein FUBP1, enhancing its stability and promoting its enrichment in the c-MYC promoter region. This leads to increased c-MYC transcription, which drives pancreatic cancer metastasis. Rescue experiments confirm that tiRNA-Val-CAC-2 promotes metastasis through FUBP1-mediated c-MYC activation. The study highlights tiRNA-Val-CAC-2 and FUBP1 as potential prognostic biomarkers and therapeutic targets for pancreatic cancer. The findings suggest that tiRNA-Val-CAC-2 may serve as a novel diagnostic and therapeutic strategy for pancreatic cancer.A study identifies tiRNA-Val-CAC-2 as a key regulator of pancreatic cancer metastasis. This tRNA-derived small RNA is significantly upregulated in metastatic pancreatic cancer tissues and serum samples from patients with metastasis. Overexpression of tiRNA-Val-CAC-2 promotes cancer cell migration and invasion, while its knockdown inhibits these processes. Mechanistically, tiRNA-Val-CAC-2 interacts with the RNA-binding protein FUBP1, enhancing its stability and promoting its enrichment in the c-MYC promoter region. This leads to increased c-MYC transcription, which drives pancreatic cancer metastasis. Rescue experiments confirm that tiRNA-Val-CAC-2 promotes metastasis through FUBP1-mediated c-MYC activation. The study highlights tiRNA-Val-CAC-2 and FUBP1 as potential prognostic biomarkers and therapeutic targets for pancreatic cancer. The findings suggest that tiRNA-Val-CAC-2 may serve as a novel diagnostic and therapeutic strategy for pancreatic cancer.