Epithelial cell polarity: a major gatekeeper against cancer?

Abstract

The correct establishment and maintenance of cell polarity are crucial for normal cell physiology and tissue homeostasis. Conversely, loss of cell polarity, tissue disorganisation and excessive cell growth are hallmarks of cancer. In this review, we focus on identifying the stages of tumoural development that are affected by the loss or deregulation of epithelial cell polarity. Asymmetric division has recently emerged as a major regulatory mechanism that controls stem cell numbers and differentiation. Links between cell polarity and asymmetric cell division in the context of cancer will be examined. Apical-basal polarity and cell-cell adhesion are tightly interconnected. Hence, how loss of cell polarity in epithelial cells may promote epithelial mesenchymal transition and metastasis will also be discussed. Altogether, we present the argument that loss of epithelial cell polarity may have an important role in both the initiation of tumourigenesis and in later stages of tumour development, favouring the progression of tumours from benign to malignancy.

Figure 1

Diagram representing the core polarity components involved in the maintenance of apical–basal polarity in epithelial cells and the establishment of membrane domain identity. AJ, adherens junctions; ALJ, apical/lateral junction; TJ, tight junctions

Figure 2

Loss of cell polarity in epithelial stem cells can lead to asymmetric division defects, thereby favouring tumour initiation. Apical–basal polarity is fundamental to the asymmetric segregation of cell fate determinants. Thick yellow and green lines represent cell fate determinants. Red dots represent centrosomes. In the absence of apical–basal polarity, this segregation is defective, potentially leading to an excess in symmetric divisions and an accumulation of cells with proliferative potential

Figure 3

Epithelial cell polarity represents a barrier to the later stages of tumour development. Apical–basal polarity is involved in the formation and maintenance of the AJC. Decreased expression of core polarity proteins is linked to weakening or disruption of the AJC, thereby leading to EMT and potential malignancy. Recent evidence suggests that TGFβ, under certain conditions, can induce EMT in epithelial cells in conjunction with loss of cell polarity

Figure 4

A summary of epithelial cell polarity's role in suppressing tumour initiation and malignancy