PPDPF promotes esophageal squamous cell carcinoma progression by blocking PCCA binding to PCCB and inhibiting methionine catabolism.

Abstract

While metabolic reprogramming and remodeling of tumor microenvironment play important roles in the development of esophageal squamous cell carcinoma (ESCC), the mechanisms remain unclear. In this study, we found that pancreatic progenitor cell differentiation and proliferation factor (PPDPF) is upregulated in ESCC and its expression level is associated with lymph node metastasis. PPDPF was found to promote tumorigenesis, lymph node metastasis and distal metastasis of ESCC cells. Furthermore, the results of mass spectrometry analysis revealed that PPDPF interacts with PCCA, the subunit of the PCC, a key enzyme involved in the catabolism of methionine by the C-Vomit pathway. In addition, PPDPF increases methionine and SAM levels. Additionally, knockdown of PPDPF decreases the levels of methionine and SAM in vivo, and promotes the infiltration of CD8⁺ T cells in ESCC. Taken together, the results of this study suggest that PPDPF inhibits the interaction between PCCA and PCCB to downregulate methionine catabolism via the C-Vomit pathway, providing a new target for the treatment of ESCC.