Thrombospondin-1 overexpression stimulates loss of Smad4 and accelerates malignant behavior via TGF-β signal activation in pancreatic ductal adenocarcinoma.

ABSTRACT:

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma and cancer-associated fibroblasts (CAFs) provide a favorable tumor microenvironment. Smad4 is known as tumor suppressor in several types of cancers including PDAC, and loss of Smad4 triggers accelerated cell invasiveness and metastatic potential. The thrombospondin-1 (TSP-1) can act as a major activator of latent transforming growth factor-β (TGF-β) in vivo. However, the roles of TSP-1 and the mediator of Smad4 loss and TGF-β signal activation during PDAC progression have not yet been addressed. The aim is to elucidate the biological role of TSP-1 in PDAC progression.

Methods and results

High substrate stiffness stimulated TSP-1 expression in CAFs, and TSP-1 knockdown inhibited cell prol

SUBMITTER: Matsumura K 

PROVIDER: S-EPMC9483797 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature