Tumor suppressor role for myopodin in bladder cancer: loss of nuclear expression of myopodin is cell-cycle dependent and predicts clinical outcome.

ABSTRACT

Myopodin is a dual compartment protein that displays actin-bundling activity and redistributes between the nucleus and the cytoplasm in a differentiation-dependent and stress-induced fashion. We evaluated myopodin expression in initiation and progression of bladder cancer. Normal urothelium expresses myopodin in the cytoplasm and nuclei. Invasive bladder tumors showed decreased nuclear myopodin expression as compared to superficial lesions. This loss of nuclear myopodin expression was significantly associated with histopathological stage, tumor grade and overall patient survival in bladder tumors contained in tissue microarrays. We identified a differential nuclear expression for myopodin among bladder cancer cell lines during cell-cycle. Myopodin was present in the nucleus during G1/S in cells derived from superficial and low-grade lesions but not in those derived from invasive tumors. Loss of nuclear myopodin expression could classify bladder tumors and bladder cancer cell lines based on their histopathology. Most importantly, patients with preserved nuclear myopodin expression showed a longer survival. Nuclear myopodin expression in the context of cell-cycle progression may prove useful for staging bladder tumors and suggest a tumor suppressor role of myopodin in bladder cancer.