We conclude that Ezrin is a key downstream factor involved in the regulation of HGF/Met signaling-induced metastasis and demonstrate a link between Ezrin and HGF/Met/MAPK/Sp1 activation in the metastatic process.
As a cortical cytoskeletal protein, ezrin adapts the cytoplasmic tail of CD44 to the actin-based cytoskeleton and is functionally involved in migration and adhesion that are prerequisites for metastasis.
These data indicate that ezrin overexpression positively correlated with metastatic potentials of human breast cancer cells, especially lymphatic system metastasis.
After universal analysis and multivariate analysis, histological type, lymph node metastasis, triple-negative breast cancer, TNM stage and distant metastasis were verified as related to Ezrin and CD44 co-expression (P=0.011, 0.006, 0.001, 0.011 and 0.001, respectively).
Collectively, our results suggest that dynamic regulation of Ezrin phosphorylation at amino acid T567 that controls structural transitions of this protein plays a pivotal role in tumor progression and metastasis, possibly in part by altering cellular metabolism.
Next, we developed a quantitative intravital microscopy (qIVM) approach, using a syngeneic lymphatic reporter mouse tumor model, to investigate the effect of systemic ezrin inhibition on cancer cell migration and metastasis.
The identification of PTHrP and ezrin as important regulators of lung cancer bone metastasis offers new mechanistic insights into the metastasis of lung cancer and provides potential targets for the prevention and treatment of lung cancer metastasis.
Recent studies show that ezrin phosphorylation regulates breast cancer metastasis by promoting cancer cell survivor and promotes intrahepatic metastasis via cell migration.
These findings indicate that ezrin and HER2 expression in patients with SGCs represents a high-grade histopathological subtype that requires adjuvant therapy, including molecularly targeted therapies, to decrease the risk of subsequent metastasis.