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. 2020 Jul 14:7:138.
doi: 10.3389/fmolb.2020.00138. eCollection 2020.

Slug and E-Cadherin: Stealth Accomplices?

Esta Sterneck  1 , Dipak K Poria  1 , Kuppusamy Balamurugan  1
Affiliations

Slug and E-Cadherin: Stealth Accomplices?

Esta Sterneck et al. Front Mol Biosci. .

Abstract

During physiological epithelial-mesenchymal transition (EMT), which is important for embryogenesis and wound healing, epithelial cells activate a program to remodel their structure and achieve a mesenchymal fate. In cancer cells, EMT confers increased invasiveness and tumor-initiating capacity, which contribute to metastasis and resistance to therapeutics. However, cellular plasticity that navigates between epithelial and mesenchymal states and maintenance of a hybrid or partial E/M phenotype appears to be even more important for cancer progression. Besides other core EMT transcription factors, the well-characterized Snail-family proteins Snail (SNAI1) and Slug (SNAI2) play important roles in both physiological and pathological EMT. Often mentioned in unison, they do, however, differ in their functions in many scenarios. Indeed, Slug expression does not always correlate with complete EMT or loss of E-cadherin (CDH1). For example, Slug plays important roles in mammary epithelial cell progenitor cell lineage commitment and differentiation, DNA damage responses, hematopoietic stem cell self-renewal, and in pathologies such as pulmonary fibrosis and atherosclerosis. In this Perspective, we highlight Slug functions in mammary epithelial cells and breast cancer as a "non-EMT factor" in basal epithelial cells and stem cells with focus reports that demonstrate co-expression of Slug and E-cadherin. We speculate that Slug and E-cadherin may cooperate in normal mammary gland and breast cancer/stem cells and advocate for functional assessment of such Slug+/E-cadherinlow/+ (SNAI2+/CDH1low/+) "basal-like epithelial" cells. Thus, Slug may be regarded as less of an EMT factor than driver of the basal epithelial cell phenotype.

Keywords: E-cadherin (CDH1); Slug (SNAI2); basal; breast cancer; epithelial-mesenchymal transition (EMT); luminal; mammary gland.

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Figures

Figure 1
Figure 1
Schematic of the mammary epithelial stem cell hierarchy depicting the known and proposed relationships of Slug and E-cadherin (see text for details). Relative differences in expression levels between cells can be assumed but are not depicted. Figure was created with BioRender.com.
Figure 2
Figure 2
Model describing expression of E-cadherin and Slug in luminal epithelial, basal epithelial and mesenchymal cancer cells and the proposed qualities of basal epithelial cancer cells due to co-expression of Slug and E-cadherin. Luminal basal transition (LBT) and basal luminal transition (BLT) are proposed terminologies in addition to EMT and MET. See text for details. Figure was created with BioRender.com.
See this image and copyright information in PMC

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