A New Role for the Mitochondrial Pro-apoptotic Protein SMAC/Diablo in Phospholipid Synthesis Associated with Tumorigenesis.

ABSTRACT: The mitochondrial pro-apoptotic protein SMAC/Diablo participates in apoptosis by negatively regulating IAPs and activating caspases, thus encouraging apoptosis. Unexpectedly, we found that SMAC/Diablo is overexpressed in cancer. This paradox was addressed here by silencing SMAC/Diablo expression using specific siRNA (si-hSMAC). In cancer cell lines and subcutaneous lung cancer xenografts in mice, such silencing reduced cell and tumor growth. Immunohistochemistry and electron microscopy of the si-hSMAC-treated residual tumor demonstrated morphological changes, including cell differentiation and reorganization into glandular/alveoli-like structures and elimination of lamellar bodies, surfactant-producing organs. Next-generation sequencing of non-targeted or si-hSMAC-treated tumors revealed a

SUBMITTER: Paul A 

PROVIDER: S-EPMC5910671 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature