cancer studies. The main reason is that only a small population
of cancer cells undergoes EMT-like processes. This is important, as bulk RNAseq for whole tumors may fail to detect an
EMT program. The phenomenon may be focal, not massive,
but importantly, focal EMT is enough to fulfill the role of the
program, cell dissemination. EMT occurs mainly at the invasion
front, and as a result of the interaction with the stroma. This is
again very similar to the situation in developing tissue in the
embryo, such as the delamination of the neural crest, occurring
only from a small region of the neural tube.
7. The confusing terms. In the last few years, reviews and textbooks
refrain from showing the two extreme E and M phenotypes
alluded above. However, together with the acceptance of the
transition process, a few terms associated with the non-extreme
phenotypes have also led to some confusion. When referred to
EMT, “metastable” alludes to the stability/plasticity of a particular state; “hybrid/intermediate” refers to the actual cell
phenotype, with simultaneous expression of both epithelial and
mesenchymal traits; and “partial” denotes the EMT process,
alluding to a partial conversion in the spectrum from E to M
or vice versa.
4 EMT Subprograms or Compatibility with Other Programs
The EMT is not only the downregulation of epithelial properties
and the upregulation of mesenchymal character, as it also includes
the ability to delaminate, move, and invade. Thus, the secretome of
the cells changes dramatically to be able to break the basement
membrane and the metabolism also changes. In addition, the
EMT has been associated with other fundamental cellular programs, including survival, proliferation, and stemness [6]. If we
think of the EMT as a global program to move cells from their
place of origin to their destinations, it is easy to understand that
cells need to arrive to their destination and therefore, be resistant to
the death signals that they may encounter in their way. Similarly, to
improve migration, cells attenuate proliferation, and the EMT has
indeed been associated with a decrease in cell division.
1. Survival. The activation of survival signaling cascades associated with EMT has many implications in physiology and
pathology. As mentioned above, the main purpose of developmental EMTs is cell dissemination and survival. Similarly, in
cancer progression, the completion of the program is dependent on the survival of the disseminated cells to be able to form
distant metastases. Importantly, the activation of resistance to
cell death has enormous implications in therapeutic strategies,
24
M. Angela Nieto
of cancer cells undergoes EMT-like processes. This is important, as bulk RNAseq for whole tumors may fail to detect an
EMT program. The phenomenon may be focal, not massive,
but importantly, focal EMT is enough to fulfill the role of the
program, cell dissemination. EMT occurs mainly at the invasion
front, and as a result of the interaction with the stroma. This is
again very similar to the situation in developing tissue in the
embryo, such as the delamination of the neural crest, occurring
only from a small region of the neural tube.
7. The confusing terms. In the last few years, reviews and textbooks
refrain from showing the two extreme E and M phenotypes
alluded above. However, together with the acceptance of the
transition process, a few terms associated with the non-extreme
phenotypes have also led to some confusion. When referred to
EMT, “metastable” alludes to the stability/plasticity of a particular state; “hybrid/intermediate” refers to the actual cell
phenotype, with simultaneous expression of both epithelial and
mesenchymal traits; and “partial” denotes the EMT process,
alluding to a partial conversion in the spectrum from E to M
or vice versa.
4 EMT Subprograms or Compatibility with Other Programs
The EMT is not only the downregulation of epithelial properties
and the upregulation of mesenchymal character, as it also includes
the ability to delaminate, move, and invade. Thus, the secretome of
the cells changes dramatically to be able to break the basement
membrane and the metabolism also changes. In addition, the
EMT has been associated with other fundamental cellular programs, including survival, proliferation, and stemness [6]. If we
think of the EMT as a global program to move cells from their
place of origin to their destinations, it is easy to understand that
cells need to arrive to their destination and therefore, be resistant to
the death signals that they may encounter in their way. Similarly, to
improve migration, cells attenuate proliferation, and the EMT has
indeed been associated with a decrease in cell division.
1. Survival. The activation of survival signaling cascades associated with EMT has many implications in physiology and
pathology. As mentioned above, the main purpose of developmental EMTs is cell dissemination and survival. Similarly, in
cancer progression, the completion of the program is dependent on the survival of the disseminated cells to be able to form
distant metastases. Importantly, the activation of resistance to
cell death has enormous implications in therapeutic strategies,
24
M. Angela Nieto