NTU Professor Co-Authors International Guidelines for Research on EMT
Epithelial–mesenchymal transition (EMT) is a crucial mechanism during early embryo development, encompassing dynamic changes in cellular organization from epithelial (E) to mesenchymal (M) phenotypes, leading to functional changes in cell migration and invasion, driven by an evolutionary conserved set of inducing signals, transcriptional regulators, and downstream effectors. EMT has been demonstrated to occur in a diverse range of physiological and pathological conditions such as tissue regeneration, tissue fibrosis, and cancer metastasis. Over the past 20 years, the EMT research field has grown exponentially. In 2019 alone, over 5,700 publications have been indexed by the Web of Science. This growing interest warrants the need for a consensus among researchers undertaking research on EMT.
The EMT International Association (TEMTIA), the official academic society for the EMT field, was established in 2003. During the 2017 biannual meeting held in Houston Texas, many EMT scholars started the idea to provide the international EMT field with clear guidelines for EMT research. After a 2-year-long discussion, the “Guidelines and Definitions for Research on Epithelial–Mesenchymal Transition” was published in April 2020 in the journal Nature Reviews Molecular Cell Biology. Prof. Ruby Yun-Ju Huang (黃韻如) of NTU’s School of Medicine was the only Taiwanese scholar among the contributing co-authors.
The guidelines recommend the following:
- EMT status cannot be assessed on the basis of one or a small number of molecular markers;
- The primary criteria for defining EMT status should be changes in cellular properties together with a set of molecular markers, rather than relying solely on molecular markers;
- EMT driving transcription factors and other molecular markers are valuable indicators of EMT, but they should be assessed in conjunction with changes in cellular characteristics to define EMT;
- Finding reliable EMT markers requires a combinatorial approach, as well as distinguishing between EMT-associated and non-EMT-associated functions.
The guidelines further emphasize a new concept, epithelial–mesenchymal plasticity (EMP), to describe the ability of cells to adopt mixed E/M features and to interconvert between intermediate E/M phenotypic states arrayed along the epithelial–mesenchymal spectrum. Prof. Huang has long been dedicated to the research of this intermediate E/M state. She defined the early events of EMT in 2012 (doi: 10.1242/jcs.099697), and in 2013 proposed the paradigm shift of the EMT concept from binary to a continuous spectrum (doi: 10.1038/cddis.2013.442). In 2014, by using big data analysis of 13,000+ cancer gene expression profiles, her group pioneered in establishing EMT signatures and defining the EMT scoring (doi: 10.15252/emmm.201404208). In 2019, her team proposed a mechanism to explain the ability to interconvert between intermediate E/M phenotypes involving the interplay of an epithelial transcription factor GRHL2 and epigenetic modifiers in CpG methylation and nucleosomal remodeling of epithelial genes (doi: 10.1038/s42003-019-0506-3).
To learn more about the EMT mechanism, please refer to NTU Speech for Prof. Ruby Yun-Ju Huang’s lecture: http://speech.ntu.edu.tw/ntuspeech/Video/id-2844.
Prof. Ruby Yun-Ju Huang is under the support of the Yushan (Young) Scholar Program, a talent recruitment initiative of the Ministry of Education, Taiwan. Her interview for the Yushan Project can be found: https://www.youtube.com/watch?v=MSgQCbDwxQE; her EMPreSS Lab at NTU: http://rubyemtspectrum.cm.ntu.edu.tw/web/home.
A schematic model illustrating the epigenetic regulation of epithelial genes in the repressed poised or active state during EMT and MET involving intermediate phenotype changes.
EMT diversity is represented by an EMP model with the accumulated loss or gain of E/M characteristics pushing a cell towards various intermediate states.