Re-expression of ABI3-binding protein suppresses thyroid tumor growth by promoting senescence and inhibiting invasion

Loss of ABI gene family member 3-binding protein (AB13BP) expression may be functionally involved in the pathogenesis of cancer. Previous reports have indicated a loss of expression in lung cancer and a presumed role in inducing cellular senescence. We show here that AB13BP expression is significantly decreased in most malignant thyroid tumors of all types. To better understand AB13BP's role, we created a model by re-expressing AB13BP in two thyroid cancer cell lines. Re-expression of AB13BP in thyroid cells resulted in a decrease in transforming activity, cell growth, cell viability, migration, invasion, and tumor growth in nude mice. AB13BP re-expression appears to trigger cellular senescence through the p2l pathway. Additionally, AB13BP induced formation of heterochromatin 1-binding protein γ-positive senescence-associated (SA) heterochromatin foci and accumulation of SA β-galactosidase. The combination of a decrease in cell growth, invasion, and other effects upon AB13BP re-expression in vitro helps to explain the large reduction in tumor growth that we observed in nude mice. Together, our data provide evidence that the loss of AB13BP expression could play a functional role in thyroid tumorigenesis. Activation of AB13BP or its pathway may represent a possible basis for targeted therapy of certain cancers.