Metastatic site influences driver gene function in pancreatic cancer.

ABSTRACT: Driver gene mutations can increase the metastatic potential of the primary tumor^1-3, but their role in sustaining tumor growth at metastatic sites is poorly understood. A paradigm of such mutations is inactivation of SMAD4 - a transcriptional effector of TGFβ signaling - which is a hallmark of multiple gastrointestinal malignancies^4,5. SMAD4 inactivation mediates TGFβ's remarkable anti- to pro-tumorigenic switch during cancer progression and can thus influence both tumor initiation and metastasis^6-14. To determine whether metastatic tumors remain dependent on SMAD4 inactivation, we developed a mouse model of pancreatic ductal adenocarcinoma (PDAC) that enables Smad4 depletion in the pre-malignant pancreas and subsequent Smad4<

SUBMITTER: Tsanov KM 

PROVIDER: S-EPMC10983983 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature