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.

Effects of silk sericin on the proliferation and apoptosis of colon cancer cells

“…The stages of apoptosis depend on differential apoptotic stimuli, as well as functions of anti-apoptotic and pro-apoptotic proteins (Indran et al, 2011;Kelly et al, 2011;Ascenzi et al, 2011). Malignant transformation of epithelial cells, including those of the colon, also involves various proteins that promote or inhibit apoptosis at different stages (Royer and Lu, 2011). Thus, it is possible that sericin might have an infl uence on some as yet unidentifi ed proteins associated with the late apoptotic stage in colon cancer cells.…”

ArhGEF18 regulates RhoA-Rock2 signaling to maintain neuro-epithelial apico-basal polarity and proliferation

“…Epithelial cells are highly polarized along their apicobasal (a-b) axis, which is crucial for both function and morphology of epithelia. A-b polarity is established and maintained by three major protein complexes: Par and Crumbs complexes are required for apical membrane identity, whereas the Scribble complex antagonizes them more basally, thus conferring basolateral identity (Royer and Lu, 2011).…”

AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

“…A strong correlation between malignancy and loss of epithelial organization has been documented for most carcinomas that may be attributed to loss of polarity 9 . The deregulation of apical-basal polarity is often depicted as a hallmark of cancer, although direct evidence, whether this is a cause or consequence of tumour progression, is not yet clear 10,11 . Evidence for a growth-suppressive role of cell polarity stems from findings in Drosophila in which the polarity proteins such as Crumbs, Scribble, Dlg and Lgl act as tumour suppressor genes 9 .…”