Discoidin domain receptor inhibitor DDR1-IN-1 induces autophagy and necroptotic cell death in malignant peripheral nerve sheath tumor.

ABSTRACT: Malignant peripheral nerve sheath tumor (MPNST) is a soft tissue sarcoma commonly associated with the tumor-predisposition disorder neurofibromatosis 1. The extracellular matrix collagens contribute to many fibrotic tumors; however, the role of collagen signaling in MPNST was unclear. This study investigated the effects of blocking the interaction between collagens and their receptors in MPNST. We first analyzed the expressions of collagen family proteins in MPNSTs and found an overall increase compared to neurofibroma. Treatment of DDR1-IN-1, a small molecule inhibitor for the collagen receptor discoidin domain receptor, induced a robust MPNST cell death, highlighting the dependence of MPNST survival on collagen signaling. DDR1-IN-1 induced MPNST cell death by activating autophagy and nec

SUBMITTER: Lai GY 

PROVIDER: S-EPMC11873111 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature