The role of lineage specifiers in pancreatic ductal adenocarcinoma

Abstract

Over the last decade, multiple genomics studies have led to the identification of discrete molecular subtypes of pancreatic ductal adenocarcinoma. A general theme has emerged that most pancreatic ductal adenocarcinoma (PDAC) can be grouped into two major subtypes based on cancer cell autonomous properties: classical/pancreatic progenitor and basal-like/squamous. The classical/progenitor subtype expresses higher levels of lineage specifiers that regulate endodermal differentiation than the basal-like/squamous subtype. The basal-like/squamous subtype confers a worse prognosis, raising the possibility that loss of these lineage specifiers might enhance the malignant potential of PDAC. Here, we discuss several of these differentially expressed lineage specifiers and examine the evidence that they might play a functional role in PDAC biology.

Keywords: Lineage specifier; molecular subtype; transcription factor.

Figure 1

Simplified schematic representation of transcriptional hierarchy and regulatory interplay between pancreatic lineage specifiers (65). The strength of these regulatory interactions appears to vary by cell type.