Tumor suppressors in Sox2-mediated lung cancers promote distinct cell-intrinsic and immunologic remodeling.

ABSTRACT: Non-small cell lung cancer (NSCLC) largely consists of lung squamous carcinoma (LUSC) and lung adenocarcinoma (LUAD). Alterations in the tumor protein p53 (TP53) and phosphatase and tensin homolog (PTEN) tumor suppressors are common in both subtypes, but their relationship with SOX2 is poorly understood. We deleted Trp53 or Pten in a C57BL/6 Sox2hi Nkx2-1-/- Lkb1-/- (SNL) genetic background and generated a highly metastatic LUSC cell line (LN2A; derived from a Sox2hi mouse model, followed by Trp53, Pten, and cyclin dependent kinase inhibitor 2A [Cdkn2a] deletion). Histologic and single-cell RNA-Seq analyses corroborated that SNL mice developed mixed tumors with both LUAD and LUSC histopathology while SNL-Trp53 and SNL-Pten mice developed LUAD and LN2A tumors that retained LUSC morphology.

SUBMITTER: Sengottuvel N 

PROVIDER: S-EPMC12220946 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature