ΔNp63α drives serine synthesis to promote carboplatin resistance in NSCLC.

ABSTRACT: Serine metabolism is a critical vulnerability in cancer; however, its role in mediating therapeutic resistance in non-small cell lung cancer (NSCLC) remains incompletely understood. In this study, we identify key enzymes in the serine synthesis pathway (SSP), namely PHGDH, PSAT1 and PSPH, as well as the serine transporter SLC1A4, which are significantly overexpressed in lung cancer and correlate with poor patient prognosis. We show that serine contributes to carboplatin resistance in NSCLC, particularly in lung squamous cell carcinoma (LUSC). Notably, the LUSC lineage-specific oncogene ΔNp63α serves as a master transcriptional regulator of serine biosynthesis, directly transactivating the expression of PHGDH, PSAT1, PSPH, and SLC1A4. ΔNp63α-driven serine biosynthesis supports nucleotide sy

SUBMITTER: Deng L 

PROVIDER: S-EPMC12920890 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature