title: A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability.
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.
authors.affiliation: IRCCS SDN, Naples, Italy.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Cantisani
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita' Federico II, Naples, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Parascandolo
authors.affiliation: Medical Biotechnology, VTT Technical Research Centre of Finland, Turku, Finland.|Center for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Merja
authors.initials: M
authors.lastname: Perälä
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita' Federico II, Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Allocca
authors.affiliation: Medical Biotechnology, VTT Technical Research Centre of Finland, Turku, Finland.|Center for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Vidal
authors.initials: V
authors.lastname: Fey
authors.affiliation: Medical Biotechnology, VTT Technical Research Centre of Finland, Turku, Finland.|Center for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Niko
authors.initials: N
authors.lastname: Sahlberg
authors.affiliation: Dipartimento di Scienze Biomediche Avanzate, Università Federico II, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Merolla
authors.affiliation: Division of Pathology, Department of Surgery, University of Pisa, Pisa, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
authors.affiliation: IRCCS SDN, Naples, Italy.
authors.forename: Mikko O
authors.initials: MO
authors.lastname: Laukkanen
authors.affiliation: FIMM-Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
authors.forename: Olli Pekka
authors.initials: OP
authors.lastname: Kallioniemi
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita' Federico II, Naples, Italy.|Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" (IEOS), C.N.R., Naples, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" (IEOS), C.N.R., Naples, Italy.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Castellone
mesh_terms: D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D034741:RNA, Small Interfering; D011494:Protein Kinases; D051096:Proto-Oncogene Proteins c-ret; D048493:Proto-Oncogene Proteins B-raf
keywords: kinases; screening; siRNA; thyroid carcinoma