PDP1 promotes the progression of breast cancer through STAT3 pathway.

This study aimed to investigate the expression pattern and mechanisms of Pyruvate Dehydrogenase Phosphatase Catalytic Subunit 1 (PDP1) in the progression of breast cancer (BC). PDP1, known for its involvement in cell energy metabolism, was found to be overexpressed in BC tissues. Notably, low PDP1 expression aligns with improved overall survival (OS) in BC patients. In this study, we found that PDP1 was overexpressed among BC tissues and low PDP1 expression showed a better prognosis for the patients with BC. PDP1 knockdown suppressed cell amplification and migration and triggered cell apoptosis in BC cells. In vivo assessments through a xenograft model unveiled the pivotal role and underlying mechanisms of PDP1 knockdown. RNA sequencing and kyoto encyclopedia of genes and genomes analysis of RNAs from PDP1 knockdown and normal MCF7 cells revealed 1440 differentially expressed genes, spotlighting the involvement of the JAK/STAT3 signaling pathway in BC progression. Western blot results implied that PDP1 knockdown led to a loss of p‐STAT3, whereas overexpression of PDP1 induced the p‐STAT3 expression. Cell counting kit‐8 assay showed that PDP1 overexpression significantly raised MDA‐MB‐231 and MCF7 cell viability while STAT3 inhibitor S3I‐201 recovered the cell growth to normal level. To summarize, PDP1 promotes the progression of BC through STAT3 pathway by regulating p‐STAT3. The findings contribute to understanding the molecular mechanisms underlying BC progression, and opening avenues for targeted therapeutic approaches. Significance statement: The purpose of this study was to investigate the expression pattern and mechanisms of Pyruvate Dehydrogenase Phosphatase Catalytic Subunit 1 (PDP1) in the progression of breast cancer (BC). Our study found that PDP1 was elevated in BC tissues, and the low PDP1 expression showed better overall survival. PDP1 could regulate cell amplification, migration, cell apoptosis and cell‐cycling progression. Knockdown of PDP1 also inhibited in vivo tumor growth. Mechanism study showed that PDP1/STAT3 signaling pathway was involved in tumor progression and PDP1 regulated cell growth via regulating the expression of p‐STAT3. Therefore, PDP1 could be a prognostic marker for identifying the BC and might be one clinical treatment target for tumor therapy. [ABSTRACT FROM AUTHOR]