Research Papers:

Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening

Maria Chiara Anania, Fabio Gasparri, Elena Cetti, Ivan Fraietta, Katia Todoerti, Claudia Miranda, Mara Mazzoni, Claudia Re, Riccardo Colombo, Giorgio Ukmar, Stefano Camisasca, Sonia Pagliardini, Marco A. Pierotti, Antonino Neri, Arturo Galvani and Angela Greco _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2015; 6:34629-34648. https://doi.org/10.18632/oncotarget.5282

Metrics: PDF 1614 views  |   HTML 2306 views  |   ?  


Maria Chiara Anania1,*, Fabio Gasparri2,*, Elena Cetti1, Ivan Fraietta2, Katia Todoerti3, Claudia Miranda1, Mara Mazzoni1, Claudia Re2, Riccardo Colombo2, Giorgio Ukmar2, Stefano Camisasca2, Sonia Pagliardini1, Marco A. Pierotti4, Antonino Neri5,6, Arturo Galvani2, Angela Greco1

1Molecular Mechanisms Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

2Cell Biology Department, Nerviano Medical Sciences Srl, Nerviano (MI), Italy

3Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy

4Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

5Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

6Hematology Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

*These authors have contributed equally to this work

Correspondence to:

Angela Greco, e-mail: [email protected]

Fabio Gasparri, e-mail: [email protected]

Keywords: thyroid cancer, non-oncogene addiction, MASTL, Cyclin D1, COPZ1

Received: June 06, 2015     Accepted: September 14, 2015     Published: September 25, 2015


The incidence of thyroid carcinoma is rapidly increasing. Although generally associated with good prognosis, a fraction of thyroid tumors are not cured by standard therapy and progress to aggressive forms for which no effective treatments are currently available. In order to identify novel therapeutic targets for thyroid carcinoma, we focused on the discovery of genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same degree for the viability of normal cells (non-oncogene addiction paradigm). We screened a siRNA oligonucleotide library targeting the human druggable genome in thyroid cancer BCPAP cell line in comparison with immortalized normal human thyrocytes (Nthy-ori 3–1). We identified a panel of hit genes whose silencing interferes with the growth of tumor cells, while sparing that of normal ones. Further analysis of three selected hit genes, namely Cyclin D1, MASTL and COPZ1, showed that they represent common vulnerabilities for thyroid tumor cells, as their inhibition reduced the viability of several thyroid tumor cell lines, regardless the histotype or oncogenic lesion. This work identified non-oncogenes essential for sustaining the phenotype of thyroid tumor cells, but not of normal cells, thus suggesting that they might represent promising targets for new therapeutic strategies.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 5282