1.16.18 Signaling Pathway Rewiring Definition

Signaling Pathway Rewiring Definition is a description of a substantial reconfiguration in the connections and relationships among the components of a cell's signaling network, in which pathways come to interact with one another, depend upon one another, or produce outputs in a pattern that differs from the network's original, normal configuration, extending beyond a simple change in the activity level of a single pathway to encompass a broader restructuring of how multiple pathways relate to one another.

Conceptual Basis

Restructuring Relationships Rather Than Simple Activity Change

Signaling pathway rewiring is defined by a change in the structural relationships connecting different pathways, such as new instances of crosstalk, altered dependency of one pathway on another, or redirection of a pathway's output toward a different downstream consequence, distinguishing rewiring from a change confined to the activity level of a single pathway considered in isolation.

A Network-Level Rather Than Pathway-Level Phenomenon

Because rewiring concerns the relationships among multiple pathways rather than the internal activity of any one pathway alone, it is best understood as a network-level phenomenon, describing how the overall architecture of interconnected signaling within a cell has been altered, rather than describing a change confined to a single, individually definable pathway.

Manifestations of Rewiring

New or Altered Crosstalk

Signaling pathway rewiring can manifest as the emergence of new crosstalk between pathways that did not previously interact, or as alteration of the strength or character of crosstalk between pathways that did previously interact, changing the degree to which activity in one pathway influences activity in another.

Altered Dependency Relationships

Signaling pathway rewiring can manifest as a change in which pathways a cell relies upon to produce a given functional outcome, such that a cellular process previously dependent primarily on one pathway becomes substantially dependent on a different pathway instead, reflecting a redistribution of functional reliance across the network.

Redirected Downstream Consequences

Signaling pathway rewiring can manifest as a change in the specific downstream consequence produced by a given pathway's activation, such that engagement of a particular pathway comes to produce a different signaling output than it would have produced under the network's original configuration.

Origins of Pathway Rewiring

Loss of a Previously Available Pathway

Rewiring can arise when a pathway that a cell previously relied upon becomes unavailable or substantially reduced in activity, prompting a compensatory shift in which other pathways come to assume a greater functional role in producing the outcomes previously governed primarily by the now-diminished pathway.

Altered Expression of Pathway Components

Rewiring can arise from changes in the relative abundance of the various components making up different signaling pathways, altering the competitive balance among pathways for shared resources or shared downstream targets, and thereby shifting the effective relationships among pathways even without any change to the individual components themselves.

Consequences of Rewiring

A Persistently Altered Signaling Network Configuration

Because rewiring restructures the relationships among pathways rather than merely adjusting the activity of a single pathway, its consequences tend to be more durable and more broadly distributed across the cell's overall signaling behavior than would result from a transient change in the activity of an individual pathway alone.

Altered Response to Pathway-Targeted Intervention

Because a rewired signaling network may no longer depend on a given pathway to the same degree as it did under its original configuration, the functional consequence of intervening upon that specific pathway can differ substantially between a cell with a normal signaling architecture and a cell whose signaling network has undergone rewiring.

Relationship to Cancer Cell Signaling Pathways

A Mechanism Underlying Broad Signaling Alteration

Signaling pathway rewiring represents a mechanism through which cancer cells can achieve widespread, coordinated alteration of their overall signaling behavior, extending the consequences of an initial change beyond a single pathway into a broader restructuring of the network as a whole.

Relevance to Variability Among Cancer Cells

Because rewiring can occur through several distinct routes and can affect different combinations of pathways within different cells, the specific pattern of signaling network rewiring present within a given cancer cell contributes to the variability observed in cancer cell signaling behavior across different cells and cell lineages.