The Popeye Domain Containing Protein 1 (POPDC1), a tight
junction-associated transmembrane protein with a unique binding site for
cAMP, has been shown to act as a tumour suppressor in cancer cells.
Through interaction with many downstream effectors and signalling
pathways, POPDC1 promotes cell adhesion and inhibits uncontrolled cell
proliferation, epithelial-to-mesenchymal transition, and metastasis.
However, POPDC1 expression is downregulated in many types of cancer,
thereby reducing its tumour-suppressive actions. This review discusses
the role of POPDC1 in the progression of the malignant phenotype and
highlights the broad range of benefits POPDC1 stabilisation may achieve
therapeutically. Cancer stem cells (CSC) are a key hallmark of
malignancies and commonly promote treatment resistance. This article
provides a comprehensive overview of CSC signalling mechanisms, many of
which have been shown to be regulated by POPDC1 in other cell types,
thus suggesting an additional therapeutic benefit for POPDC1-stabilising