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 (ABI3BP) 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 ABI3BP expression is significantly decreased in most malignant thyroid tumors of all types. To better understand ABI3BP's role, we created a model by re-expressing ABI3BP in two thyroid cancer cell lines. Re-expression of ABI3BP in thyroid cells resulted in a decrease in transforming activity, cell growth, cell viability, migration, invasion, and tumor growth in nude mice. ABI3BP re-expression appears to trigger cellular senescence through the p21 pathway. Additionally, ABI3BP induced formation of heterochromatin 1-binding protein gamma-positive senescence-associated (SA) heterochromatin foci and accumulation of SA beta-galactosidase. The combination of a decrease in cell growth, invasion, and other effects upon ABI3BP 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 ABI3BP expression could play a functional role in thyroid tumorigenesis. Activation of ABI3BP or its pathway may represent a possible basis for targeted therapy of certain cancers.
Latini
Flavia R M
FR
Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, Brazil.
Hemerly
Jefferson P
JP
Oler
Gisele
G
Riggins
Gregory J
GJ
Cerutti
Janete M
JM
D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D014162:Transfection; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
C439569:ABI3BP protein, human; D002352:Carrier Proteins