The more we look, the more diverse cell morphologies and
migration modes appear. Single cells can move not only in a
fibroblast-like, mesenchymal mode but also in a blebbing manner
sometimes referred to as amoeboid or myeloid. Cells can transition
between these different modes as well. To the EMT, we must add
the epithelial to amoeboid transition, the amoeboid to mesenchymal transition, the mesenchymal to amoeboid transition, etc.
[14]. Some collective cell migrations, such as border cell migration,
which we study in my laboratory, do not involve any form of an
EMT [15]. These six epithelial cells do not express Twist or Snail.
They maintain apicobasal polarity even while acquiring leading/
lagging migratory polarity. They require increased rather than
decreased E-cadherin expression to move. They remain connected
to one another by adherens and gap junctions. One might be
tempted to dismiss these cells as a quirk of fly biology, except that
they look an awful lot like the tumor cell clusters that seed metastases [8, 10].
3 Moving Forward
So how should we think about cell motility in normal development
and in cancer? It is more complex than we originally envisioned.
But is it infinitely complex and incomprehensible? I don’t think
so. Everywhere we look, nature builds complexity from simple,
modular components. To return to DNA, our remarkably complex
genetic information, for example, is encoded by just four nucleotides, used in combination. Genes themselves are built from modular exons. The byzantine regulation of gene expression that drives
embryonic development is accomplished by combinatorial use of
simple, modular enhancers. Tens of thousands of proteins are built
from just 20 amino acids. Complex organs and animals are built
from simpler organizational units like the nephron or vertebrae.
Throughout biology, and at multiple scales, complexity arises from
the combinatorial deployment of simple, modular components.
Kind of like Legos.
Perhaps then, nature also builds complexity and diversity in
cellular morphology and behavior from combinations of modules.
But what modules? Ultimately the shapes and behaviors of cells are
determined by forces. So one idea is that cellular morphologies and
behaviors are produced by combinations of simple and modular
forces [16](Fig. 1). Consider four force-generating properties of
cells: protrusion, contractility, cell-cell cohesion, and cell-matrix
adhesion. I propose that the shape of a single cell and the arrangement of a group of cells are determined in large measure by the
relative strengths and localizations of these four forces as illustrated
in Fig. 1.
EMT, One of Many Morphological Transitions in Cellular Phase Space
15
migration modes appear. Single cells can move not only in a
fibroblast-like, mesenchymal mode but also in a blebbing manner
sometimes referred to as amoeboid or myeloid. Cells can transition
between these different modes as well. To the EMT, we must add
the epithelial to amoeboid transition, the amoeboid to mesenchymal transition, the mesenchymal to amoeboid transition, etc.
[14]. Some collective cell migrations, such as border cell migration,
which we study in my laboratory, do not involve any form of an
EMT [15]. These six epithelial cells do not express Twist or Snail.
They maintain apicobasal polarity even while acquiring leading/
lagging migratory polarity. They require increased rather than
decreased E-cadherin expression to move. They remain connected
to one another by adherens and gap junctions. One might be
tempted to dismiss these cells as a quirk of fly biology, except that
they look an awful lot like the tumor cell clusters that seed metastases [8, 10].
3 Moving Forward
So how should we think about cell motility in normal development
and in cancer? It is more complex than we originally envisioned.
But is it infinitely complex and incomprehensible? I don’t think
so. Everywhere we look, nature builds complexity from simple,
modular components. To return to DNA, our remarkably complex
genetic information, for example, is encoded by just four nucleotides, used in combination. Genes themselves are built from modular exons. The byzantine regulation of gene expression that drives
embryonic development is accomplished by combinatorial use of
simple, modular enhancers. Tens of thousands of proteins are built
from just 20 amino acids. Complex organs and animals are built
from simpler organizational units like the nephron or vertebrae.
Throughout biology, and at multiple scales, complexity arises from
the combinatorial deployment of simple, modular components.
Kind of like Legos.
Perhaps then, nature also builds complexity and diversity in
cellular morphology and behavior from combinations of modules.
But what modules? Ultimately the shapes and behaviors of cells are
determined by forces. So one idea is that cellular morphologies and
behaviors are produced by combinations of simple and modular
forces [16](Fig. 1). Consider four force-generating properties of
cells: protrusion, contractility, cell-cell cohesion, and cell-matrix
adhesion. I propose that the shape of a single cell and the arrangement of a group of cells are determined in large measure by the
relative strengths and localizations of these four forces as illustrated
in Fig. 1.
EMT, One of Many Morphological Transitions in Cellular Phase Space
15