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Review
. 2023 Aug 3:14:1207360.
doi: 10.3389/fimmu.2023.1207360. eCollection 2023.

An "unexpected" role for EMT transcription factors in hematological development and malignancy

Karthika Radhakrishnan  1 , Lynda Truong  1 , Catherine L Carmichael  1   2
Affiliations
Review

An "unexpected" role for EMT transcription factors in hematological development and malignancy

Karthika Radhakrishnan et al. Front Immunol. .

Abstract

The epithelial to mesenchymal transition (EMT) is a fundamental developmental process essential for normal embryonic development. It is also important during various pathogenic processes including fibrosis, wound healing and epithelial cancer cell metastasis and invasion. EMT is regulated by a variety of cell signalling pathways, cell-cell interactions and microenvironmental cues, however the key drivers of EMT are transcription factors of the ZEB, TWIST and SNAIL families. Recently, novel and unexpected roles for these EMT transcription factors (EMT-TFs) during normal blood cell development have emerged, which appear to be largely independent of classical EMT processes. Furthermore, EMT-TFs have also begun to be implicated in the development and pathogenesis of malignant hematological diseases such as leukemia and lymphoma, and now present themselves or the pathways they regulate as possible new therapeutic targets within these malignancies. In this review, we discuss the ZEB, TWIST and SNAIL families of EMT-TFs, focusing on what is known about their normal roles during hematopoiesis as well as the emerging and "unexpected" contribution they play during development and progression of blood cancers.

Keywords: EMT; blood cells; hematopoiesis; leukemia; malignancy; stem cells.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
EMT-TF expression in hematopoiesis: Generalized overview of EMT-TFs expression throughout the hematopoietic hierarchy, as outlined in referenced articles. In many cases expression of EMT-TFs has not been thoroughly assessed experimentally, and current knowledge relies on gene expression datasets obtained from sorted mouse and/or human cells. Created with BioRender.com.
Figure 2
Figure 2
ZEB family roles in hematopoiesis: Schematic showing known functions of ZEB1 and ZEB2 during normal hematopoiesis as determined through analysis of knockout mouse models. Created with BioRender.com.
Figure 3
Figure 3
TWIST family roles in hematopoiesis: Schematic showing known functions of TWIST1 and TWIST2 during normal hematopoiesis as determined through analysis of knockout mouse models. Created with BioRender.com.
Figure 4
Figure 4
SNAIL family roles in hematopoiesis: Schematic showing known functions of SNAI1, SNAI2 and SNAI3 during normal hematopoiesis as determined through analysis of knockout mouse models. Created with BioRender.com.
Figure 5
Figure 5
ZEB family during malignant hematopoiesis: Schematic outlining ZEB family roles in malignant hematopoiesis as determined through human and mouse model analyses. Created with BioRender.com.
Figure 6
Figure 6
TWIST family during malignant hematopoiesis: Schematic outlining TWIST family roles in malignant hematopoiesis as determined through human and mouse model analyses. Created with BioRender.com.
Figure 7
Figure 7
SNAIL family during malignant hematopoiesis: Schematic outlining SNAIL family roles in malignant hematopoiesis as determined through human and mouse model analyses. Created with BioRender.com.
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Grants and funding

CC is supported by National Health and Medical Research Council Ideas Grant funding (GNT1182318), and a Victorian Cancer Agency Mid-Career Fellowship (MCRF22015).
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