their final destinations, a solution that was found to help cells move
leaving behind their tissue of origin [6]. Importantly, all metazoans
throughout evolution have used EMT-like processes as the mechanism for cell dissemination and survival. Thus, it seems very reasonable that this mechanism is also used by cancer cells, and can be
regarded as a pathological reactivation of a crucial developmental
program.
2 The Intrinsic Complexity/Heterogeneity: Do Not Be Afraid
One of the main reasons why some researchers are disillusioned and
not very interested in studying EMT is the complexity of the
process. Indeed, EMT is complex: it is induced by multiple extracellular cellular signals; the signals converge in a plethora of transcription factors (EMT-TFs) and how these factors implement the
EMT program is not so evident. Perhaps the best way to look at it is
to think of commonalities, just going back to the main purpose of
the process: cell dissemination and survival.
The EMT is all about how to achieve cell dissemination in an
efficient manner, with the requirement that cells reach their final
destination. In other words, that cells survive till the end of the
journey. How this is implemented depends on the cellular context.
And here there is the second unwanted word: context-dependent.
For many researchers, this may just indicate that we do not know
much about the process. The answer is however much more interesting. Evolution has provided us with the richness of biology
which, in this particular context, implies the existence of many
EMT transcription factors that trigger the expression of a plethora
of target genes. How these EMT-TFs operate is still a matter of
active investigation, with both commonalities and specificities to
the programs they can implement individually or in combination.
This enables cells to deal with the different topologies and microenvironments that they encounter while disseminating, both in
development and cancer. As a result of that, both embryonic and
cancer cells express combinations of EMT-TFs, an EMT-TF code.
Importantly, cell behavior will be the outcome of the specific
EMT-TF code implemented by the signaling inputs. In cancer,
this heterogeneity adds another level of complexity to that provided
by mutations and genomic instability, with implications for the
design and interpretation of experiments in the field. For instance,
loss of function analysis for a single EMT factor cannot be taken as
surrogate of the whole EMT process, as different developing tissues
and carcinomas use different EMT programs [7, 8]. Thus, do not be
afraid, pay attention to the commonalities, but characterize the system
by examining the expression code in the tissue/tumor of interest.
20
M. Angela Nieto
leaving behind their tissue of origin [6]. Importantly, all metazoans
throughout evolution have used EMT-like processes as the mechanism for cell dissemination and survival. Thus, it seems very reasonable that this mechanism is also used by cancer cells, and can be
regarded as a pathological reactivation of a crucial developmental
program.
2 The Intrinsic Complexity/Heterogeneity: Do Not Be Afraid
One of the main reasons why some researchers are disillusioned and
not very interested in studying EMT is the complexity of the
process. Indeed, EMT is complex: it is induced by multiple extracellular cellular signals; the signals converge in a plethora of transcription factors (EMT-TFs) and how these factors implement the
EMT program is not so evident. Perhaps the best way to look at it is
to think of commonalities, just going back to the main purpose of
the process: cell dissemination and survival.
The EMT is all about how to achieve cell dissemination in an
efficient manner, with the requirement that cells reach their final
destination. In other words, that cells survive till the end of the
journey. How this is implemented depends on the cellular context.
And here there is the second unwanted word: context-dependent.
For many researchers, this may just indicate that we do not know
much about the process. The answer is however much more interesting. Evolution has provided us with the richness of biology
which, in this particular context, implies the existence of many
EMT transcription factors that trigger the expression of a plethora
of target genes. How these EMT-TFs operate is still a matter of
active investigation, with both commonalities and specificities to
the programs they can implement individually or in combination.
This enables cells to deal with the different topologies and microenvironments that they encounter while disseminating, both in
development and cancer. As a result of that, both embryonic and
cancer cells express combinations of EMT-TFs, an EMT-TF code.
Importantly, cell behavior will be the outcome of the specific
EMT-TF code implemented by the signaling inputs. In cancer,
this heterogeneity adds another level of complexity to that provided
by mutations and genomic instability, with implications for the
design and interpretation of experiments in the field. For instance,
loss of function analysis for a single EMT factor cannot be taken as
surrogate of the whole EMT process, as different developing tissues
and carcinomas use different EMT programs [7, 8]. Thus, do not be
afraid, pay attention to the commonalities, but characterize the system
by examining the expression code in the tissue/tumor of interest.
20
M. Angela Nieto