Phenotypic Plasticity of Cancer Cells Based on Remodeling of the Actin Cytoskeleton and Adhesive Structures

There is ample evidence that, instead of a binary switch, epithelial-mesenchymal transition (EMT) in cancer results in a flexible array of phenotypes, each one uniquely suited to a stage in the invasion-metastasis cascade. The phenotypic plasticity of epithelium-derived cancer cells gives them an edge in surviving and thriving in alien environments. This review describes in detail the actin cytoskeleton and E-cadherin-based adherens junction rearrangements that cancer cells need to implement in order to achieve the advantageous epithelial/mesenchymal phenotype and plasticity of migratory phenotypes that can arise from partial EMT.

Coincidence of Homeostasis and Bifurcation in Feedforward Networks

Homeostasis is an important and common biological phenomenon wherein an output variable does not change very much as an input parameter is varied over an interval. It can be studied by restricting attention to homeostasis points — points where the output variable has a vanishing derivative with respect to the input parameter. In a feedforward network, if a node has a homeostasis point then downstream nodes will inherit it. This is the case except when the downstream node has a bifurcation point coinciding with the homeostasis point. We apply singularity theory to study the behavior of the downstream node near these homeostasis-bifurcation points. The unfoldings of low codimension homeostasis-bifurcation points are found. In the case of steady-state bifurcation, the behavior includes multiple homeostatic plateaus separated by hysteretic switches. In the case of Hopf bifurcation, the downstream node may have limit cycles with a wide range of near-constant amplitudes and periods. Homeostasis-bifurcation is therefore a mechanism by which binary, switch-like responses or stable clock rhythms could arise in biological systems.

Molecular Mechanisms Driving Bistable Switch Behavior in Xylem Cell Differentiation

SummaryPlant xylem cells conduct water and mineral nutrients. Although most plant cells are totipotent, xylem cells are unusual and undergo terminal differentiation. Many genes regulating this process are well characterized, including the VASCULAR-RELATED NAC DOMAIN7 (VND7), MYB46 and MYB83 transcription factors which are proposed to act in interconnected feed-forward loops. Much less is known regarding the dynamic behavior underlying the terminal transition to xylem cell differentiation. Here we utilize whole root and single cell data to mathematically model this relationship. These provide evidence for VND7 regulating bistable switching of cells in the root to a xylem cell identity, with additional features of hysteresis. We further determine that although MYB46 responds to VND7 induction, it is not inherently involved in executing the binary switch. A novel regulatory architecture is proposed that involves four downstream targets of VND7 that act in a cycle. These data provide an important model to study the emergent properties that may give rise to totipotency relative to terminal differentiation and reveal novel xylem cell subtypes.

How can a binary switch within the pars tuberalis control seasonal timing of reproduction?

Life in seasonally changing environments is challenging. Biological systems have to not only respond directly to the environment, but also schedule life history events in anticipation of seasonal changes. The cellular and molecular basis of how these events are scheduled is unknown. Cellular decision-making processes in response to signals above certain thresholds regularly occur i.e. cellular fate determination, apoptosis and firing of action potentials. Binary switches, the result of cellular decision-making processes, are defined as a change in phenotype between two stable states. A recent study presents evidence of a binary switch operating in the pars tuberalis (PT) of the pituitary, seemingly timing seasonal reproduction in sheep. Though, how a binary switch would allow for anticipation of seasonal environmental changes, not just direct responsiveness, is unclear. The purpose of this review is to assess the evidence for a binary switching mechanism timing seasonal reproduction and to hypothesize how a binary switch would allow biological processes to be timed over weeks to years. I draw parallels with mechanisms used in development, cell fate determination and seasonal timing in plants. I propose that the adult PT is a plastic tissue, showing a seasonal cycle of cellular differentiation, and that the underlying processes are likely to be epigenetic. Therefore, considering the mechanisms behind adult cellular plasticity offers a framework to hypothesize how a long-term timer functions within the PT.