A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability
| Autor: | Niko Sahlberg, Alessia Parascandolo, Massimo Santoro, Maria Carmela Cantisani, Vidal Fey, Francesco Merolla, Olli Kallioniemi, Chiara Allocca, Maria Domenica Castellone, Merja Perälä, Mikko O. Laukkanen, Fulvio Basolo |
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| Přispěvatelé: | Cantisani, MARIA CARMELA, Parascandolo, Alessia, Perälä, Merja, Allocca, Chiara, Fey, Vidal, Sahlberg, Niko, Merolla, Francesco, Basolo, Fulvio, Laukkanen, Mikko O, Kallioniemi, Olli Pekka, Santoro, Massimo, Castellone, Maria Domenica |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Proto-Oncogene Proteins B-raf Kinases Screening siRNA Thyroid carcinoma Oncology endocrine system endocrine system diseases kinase Cell Survival ta3111 Papillary thyroid cancer 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being Cell Line Tumor medicine Humans Kinome Thyroid Neoplasms Anaplastic thyroid cancer RNA Small Interfering Thyroid cancer Cell Proliferation business.industry Kinase screening Proto-Oncogene Proteins c-ret ta1182 medicine.disease ta3122 thyroid carcinoma Carcinoma Papillary 3. Good health Gene Expression Regulation Neoplastic 030104 developmental biology kinases 030220 oncology & carcinogenesis Cancer cell Immunology Cancer research RNA Interference business Protein Kinases Research Paper |
| Zdroj: | Oncotarget Cantisani, M C, Parascandolo, A, Perälä, M, Allocca, C, Fey, V, Sahlberg, N, Merolla, F, Basolo, F, Laukkanen, M O, Kallioniemi, O P, Santoro, M & Castellone, M D 2016, ' A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability ', Oncotarget, vol. 7, no. 19, pp. 28510-28522 . https://doi.org/10.18632/oncotarget.8577 |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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