The Wnt/β-catenin pathway is an evolutionarily conserved developmental pathway involved in several physiological processes. Aberrant activation of the Wnt/β-catenin pathway is implicated in many tumor types. Active β-catenin, a key protein in the Wnt pathway, can trigger the transcription of important regulators of cell cycle progression, cell proliferation and cell stemness upon activation and nuclear translocation.
The immunohistochemical detection of β-catenin with specific antibodies for the active form is a powerful tool for the assessment of total active β-catenin in a given sample. However, the inclusion of a mechanism designed for the specific detection of the nuclear fraction of Active β-catenin could improve the global usefulness of the technique.
In this report, we simultaneously assessed, for the first time, total and nuclear accumulation of β-catenin by a systems biology approach applying a multiplex immunofluorescent assay to a cohort of 506 prostate cancer patients from three different hospitals. Our data shows that nuclear and total Active β-catenin accumulation is significantly lower in adjacent normal areas when compared to tumor areas of the same patients (p<0.001).
In conclusion, our systems biology-based approach allows the discrimation between the effector fraction (i.e. nuclear) and the non-effector form of total active β-catenin. This is a new tool for a precise quantification of the nuclear active β-catenin fraction. The present work supports the activation of the Wnt/β-catenin pathway in prostate cancer progression measured as total and nuclear accumulation of active β-catenin.