The CPT1A/Snail axis promotes pancreatic adenocarcinoma progression and metastasis by activating the glycolytic pathway
Shipeng Yang,
Ying Liu,
Chunxiao Tang,
Anna Han,
Zhenhua Lin,
Jishu Quan,
Yang Yang
Affiliations
Shipeng Yang
Central Laboratory, The Affiliated Hospital of Yanbian University, Yanji 133000, China; Key Laboratory of Tumor Pathobiology (Yanbian University), State Ethnic Affairs, Commission, Yanji 133000, China; Department of Pathology, Yanbian University Medical College, Yanji 133000, China
Ying Liu
Key Laboratory of Tumor Pathobiology (Yanbian University), State Ethnic Affairs, Commission, Yanji 133000, China
Chunxiao Tang
Key Laboratory of Tumor Pathobiology (Yanbian University), State Ethnic Affairs, Commission, Yanji 133000, China
Anna Han
Key Laboratory of Tumor Pathobiology (Yanbian University), State Ethnic Affairs, Commission, Yanji 133000, China
Zhenhua Lin
Central Laboratory, The Affiliated Hospital of Yanbian University, Yanji 133000, China; Key Laboratory of Tumor Pathobiology (Yanbian University), State Ethnic Affairs, Commission, Yanji 133000, China
Jishu Quan
Key Laboratory of Tumor Pathobiology (Yanbian University), State Ethnic Affairs, Commission, Yanji 133000, China
Yang Yang
Central Laboratory, The Affiliated Hospital of Yanbian University, Yanji 133000, China; Key Laboratory of Tumor Pathobiology (Yanbian University), State Ethnic Affairs, Commission, Yanji 133000, China; Department of Pathology, Yanbian University Medical College, Yanji 133000, China; Corresponding author
Summary: Recent studies have demonstrated that CPT1A plays a critical role in tumor metabolism and progression. However, the molecular mechanisms by which CPT1A affects tumorigenicity during PAAD progression remain unclear. In the current research, the bioinformatics analysis and immunohistochemical staining results showed that CPT1A was overexpressed in PAAD tissues and that its overexpression was associated with a shorter survival time in patients with PAAD. Overexpression of CPT1A increased cell proliferation and promoted EMT and glycolytic metabolism in PAAD cells. Mechanistically, CPT1A is able to bind to Snail and facilitate PAAD progression by regulating Snail stability. In summary, our findings revealed Snail-dependent glycolysis as a crucial metabolic pathway by which CPT1A accelerates PAAD progression. Targeting the CPT1A/Snail/glycolysis axis in PAAD to suppress cell proliferation and metastatic dissemination is a new potential treatment strategy to improve the anticancer therapeutic effect and prolong patient survival.
