Targeting matrix metalloproteinase-14 disrupts DNA repair and reduces viability in adrenocortical carcinoma.

ABSTRACT:

Background

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine cancer with limited treatment options and poor prognosis. Identifying novel therapeutic targets requires understanding the molecular drivers of ACC progression and establishing translational models for preclinical validation.

Results

Matrix metalloproteinase-14 (MMP-14) is the most highly expressed MMP in ACC, and high MMP-14 expression is associated with worse overall and disease-free survival. We demonstrate that MMP-14 is essential for ACC cell survival and serves an unexpected role in maintaining genome stability. Genetic silencing or pharmacologic inhibition of MMP-14 significantly reduced viability in both NCI-H295R cells and patient-derived tumor organoids (PTOs). MMP-14 knockdown induced CHK

SUBMITTER: Shen C 

PROVIDER: S-EPMC12803226 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature