betacatenindependent

Beta-catenin-independent, or beta-catenin–independent signaling, refers to signaling pathways that do not rely on stabilization and transcriptional activity of β-catenin. In contrast to the canonical Wnt/β-catenin pathway, these routes operate through alternative effectors to regulate cell behavior, polarity, movement, and calcium signaling without activating β-catenin–dependent gene transcription.

A prominent example is noncanonical Wnt signaling, which is activated by Wnt ligands such as Wnt5a and Wnt11 and typically does not stabilize β-catenin. The planar cell polarity (PCP) pathway, a major branch of noncanonical signaling, uses core components like Dishevelled, Frizzled receptors, Vangl, Prickle, and Flamingo to control cytoskeletal organization and cell orientation. PCP signaling influences convergent extension movements during embryogenesis, tissue morphogenesis, and cell migration in various contexts.

Another noncanonical route is the Wnt/Ca2+ pathway, in which Wnt engagement leads to increases in intracellular calcium. This can activate calcium-dependent enzymes such as calcineurin and CaMKII, modulate transcription via NFAT, and affect processes like adhesion, adhesion turnover, and neuronal signaling. Receptors involved are typically Frizzleds in combination with specific co-receptors, and downstream responses may be context-dependent.

These beta-catenin-independent pathways can cross-talk with other signaling networks and may interact with canonical signaling under certain conditions. They are particularly important for directing cell polarity, migration, and tissue organization during development and in wound healing, and their misregulation has been linked to cancer metastasis and developmental disorders. The term noncanonical Wnt signaling is commonly used to describe these beta-catenin-independent routes.