Oncotarget

Research Papers:

A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability

Maria Carmela Cantisani, Alessia Parascandolo, Merja Perälä, Chiara Allocca, Vidal Fey, Niko Sahlberg, Francesco Merolla, Fulvio Basolo, Mikko O. Laukkanen, Olli Pekka Kallioniemi, Massimo Santoro and Maria Domenica Castellone _

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Oncotarget. 2016; 7:28510-28522. https://doi.org/10.18632/oncotarget.8577

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Abstract

Maria Carmela Cantisani1, Alessia Parascandolo2, Merja Perälä3,4, Chiara Allocca2, Vidal Fey3,4, Niko Sahlberg3,4, Francesco Merolla5, Fulvio Basolo6, Mikko O. Laukkanen1, Olli Pekka Kallioniemi7, Massimo Santoro2,8, Maria Domenica Castellone8

1IRCCS SDN, Naples, Italy

2Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita’ Federico II, Naples, Italy

3Medical Biotechnology, VTT Technical Research Centre of Finland, Turku, Finland

4Center for Biotechnology, University of Turku, Turku, Finland

5Dipartimento di Scienze Biomediche Avanzate, Università Federico II, Naples, Italy

6Division of Pathology, Department of Surgery, University of Pisa, Pisa, Italy

7FIMM-Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland

8Istituto di Endocrinologia ed Oncologia Sperimentale “G. Salvatore” (IEOS), C.N.R., Naples, Italy

Correspondence to:

Maria Domenica Castellone, e-mail: [email protected]

Keywords: kinases, screening, siRNA, thyroid carcinoma

Received: October 01, 2015     Accepted: March 02, 2016     Published: April 4, 2016

ABSTRACT

RET, BRAF and other protein kinases have been identified as major molecular players in thyroid cancer. To identify novel kinases required for the viability of thyroid carcinoma cells, we performed a RNA interference screening in the RET/PTC1(CCDC6-RET)-positive papillary thyroid cancer cell line TPC1 using a library of synthetic small interfering RNAs (siRNAs) targeting the human kinome and related proteins. We identified 14 hits whose silencing was able to significantly reduce the viability and the proliferation of TPC1 cells; most of them were active also in BRAF-mutant BCPAP (papillary thyroid cancer) and 8505C (anaplastic thyroid cancer) and in RAS-mutant CAL62 (anaplastic thyroid cancer) cells. These included members of EPH receptor tyrosine kinase family as well as SRC and MAPK (mitogen activated protein kinases) families. Importantly, silencing of the identified hits did not affect significantly the viability of Nthy-ori 3-1 (hereafter referred to as NTHY) cells derived from normal thyroid tissue, suggesting cancer cell specificity. The identified proteins are worth exploring as potential novel druggable thyroid cancer targets.


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