HOXC8 impacts lung tumorigenesis by preventing pyroptotic cell death through the suppression of caspase-1 expression.

ABSTRACT: Homeobox C8 (HOXC8) is a transcription factor preferentially overexpressed in a large percentage of non-small cell lung carcinoma (NSCLC). To investigate the function of HOXC8 in NSCLC, we showed that knockdown of HOXC8 led to massive NSCLC cell death in a mechanism of pyroptosis because both YVAD, a caspase-1 (CASP1) inhibitor, and disulfiram, which prevents gasdermin D (GSDMD) pore formation, blocked cell death caused by HOXC8 depletion. Intriguingly, ASC, a key component of canonic inflammasome, was dispensable for pyroptosis occurring in HOXC8-depleted cells. Instead, we detected greatly elevated levels of both CASP1 protein and mRNA in HOXC8-knockdown cells. As forced expression of CASP1 is sufficient to induce CASP1 activation and pyroptosis, we reason that pyroptosis led by HOXC8 de

SUBMITTER: Padia R 

PROVIDER: S-EPMC12287344 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature