Abstract
Epithelial-mesenchymal plasticity (EMP) underlies embryonic development, wound healing, and cancer metastasis and fibrosis. Cancer cells exhibiting EMP often have more aggressive behavior, characterized by drug resistance, and tumor-initiating and immuno-evasive traits. Thus, the EMP status of cancer cells can be a critical indicator of patient prognosis. Here, we compare three distinct transcriptomic-based metrics—each derived using a different gene list and algorithm—that quantify the EMP spectrum. Our results for over 80 cancer-related RNA-seq datasets reveal a high degree of concordance among these metrics in quantifying the extent of EMP. Moreover, each metric, despite being trained on cancer expression profiles, recapitulates the expected changes in EMP scores for non-cancer contexts such as lung fibrosis and cellular reprogramming into induced pluripotent stem cells. Thus, we offer a scoring platform to quantify the extent of EMP in vitro and in vivo for diverse biological applications including cancer.
Highlights
Characterizing the Epithelial-mesenchymal plasticity (EMP) as a continuous spectrum instead of as an “all-or-none” process becomes imperative for an improved understanding of the emergent dynamics of EMT and MET, and their relevance to patient survival
We used three different EMT transcriptomic-based scoring metrics, each of which was developed using cancer cell lines and/or tumor samples and tested on microarray data previously to quantify the extent of EMT in a continuum—76GS, KS, multinomial logistic regression (MLR)
We calculated EMT scores for over 100 RNA-seq datasets—including at bulk and single-cell levels—across multiple biological contexts (cancer (Figures 2 and 3), fibrosis, chronic obstructive pulmonary disease (COPD), and cellular reprogramming to induced pluripotent stem cells (iPSCs) (Figure 4))
Summary
EMP involves dynamic and reversible switching among multiple phenotypes along the epithelial-hybrid-mesenchymal spectrum. EMP usually entails changes in cell–cell adhesion, migration, and invasion; while EMT is often involved with cells escaping the primary tumor and initiating metastasis, MET is thought to be important for colonization, the last step of metastasis. Besides these features, EMP is implicated in conferring tumor-initiation potential [5,6], immune evasion [7,8,9], and resistance to various chemotherapeutic drugs and targeted therapies [10,11,12]. EMP can be considered as published maps and institutional affiliations
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
