Beyond just a tight fortress: contribution of stroma to epithelial-mesenchymal transition in pancreatic cancer

Ashenafi Bulle, Kian Huat Lim

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

Novel effective treatment is direly needed for patients with pancreatic ductal adenocarcinoma (PDAC). Therapeutics that target the driver mutations, especially the KRAS oncoprotein and its effector cascades, have been ineffective. It is increasing clear that the extensive fibro-inflammatory stroma (or desmoplasia) of PDAC plays an active role in the progression and therapeutic resistance of PDAC. The desmoplastic stroma is composed of dense extracellular matrix (ECM) deposited mainly by the cancer-associated-fibroblasts (CAFs) and infiltrated with various types of immune cells. The dense ECM functions as a physical barrier that limits tumor vasculatures and distribution of therapeutics to PDAC cells. In addition, mounting evidence have demonstrated that both CAFs and ECM promote PDAC cells aggressiveness through multiple mechanisms, particularly engagement of the epithelial-mesenchymal transition (EMT) program. Acquisition of a mesenchymal-like phenotype renders PDAC cells more invasive and resistant to therapy-induced apoptosis. Here, we critically review seminal and recent articles on the signaling mechanisms by which each stromal element promotes EMT in PDAC. We discussed the experimental models that are currently employed and best suited to study EMT in PDAC, which are instrumental in increasing the chance of successful clinical translation.

Original languageEnglish
Article number249
JournalSignal Transduction and Targeted Therapy
Volume5
Issue number1
DOIs
StatePublished - Dec 1 2020

Fingerprint Dive into the research topics of 'Beyond just a tight fortress: contribution of stroma to epithelial-mesenchymal transition in pancreatic cancer'. Together they form a unique fingerprint.

Cite this