S100A11 overexpression contributes to the malignant phenotype of papillary thyroid carcinoma.
BACKGROUND
Papillary thyroid carcinoma (PTC) is the most frequent thyroid tumor and is responsible for the overall increase in thyroid cancer incidence. S100A11 (calgizzarin), a member of the S100 Ca(2+)-binding protein family, is involved in several different biological processes. S100A11 has been found up-regulated in PTC, both at the mRNA and protein levels.


OBJECTIVE
Through a combination of expression analysis and functional in vitro and in vivo studies, we have attempted to gain insight into the relevance of S100A11 overexpression in PTC biology.


METHODS
The expression of the S100A11 gene in PTC was investigated in several gene expression data sets. The effect of S100A11 silencing on the hallmarks of the malignant phenotype of several PTC-derived cell lines was investigated. In NIH3T3 cells, the cooperation of S100A11 with the different PTC-specific oncogenes was assessed.


RESULTS
We found that the S100A11 gene expression is frequently up-regulated in PTC, anaplastic thyroid carcinoma, but not in follicular thyroid carcinoma. S100A11 overexpression was also detected in PTC-derived cell lines, which were then used for functional studies. S100A11 silencing in PTC-derived cell lines did not affect cell proliferation, whereas it reduced the loss of contact inhibition, anchorage-independent growth, and resistance to anoikis. Cotransfection experiments in NIH3T3 cells showed that overexpression of the S100A11 gene was able to enhance the transforming capabilities of the different PTC-associated oncogenes by affecting the loss of contact inhibition, anchorage-independent growth, and in vivo tumor formation.


CONCLUSIONS
Our data indicate that S100A11 overexpression exerts a protumoral functional role in PTC pathogenesis.
PhD, Fondazione IRCCS, Istituto Nazionale dei Tumori, Via G. A. Amadeo, 42 20133 Milan, Italy. angela.greco@istitutotumori.mi.it.
Maria Chiara
MC
Anania
Claudia
C
Miranda
Maria Grazia
MG
Vizioli
Mara
M
Mazzoni
Loredana
L
Cleris
Sonia
S
Pagliardini
Giacomo
G
Manenti
Maria Grazia
MG
Borrello
Marco Alessandro
MA
Pierotti
Angela
A
Greco
D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000473:pathology; D000818:Animals; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D009418:S100 Proteins / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation
D009418:S100 Proteins; C072337:S100A11 protein, human