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, Maria Domenica Castellone

Research output: Contribution to journalArticleScientificpeer-review

10 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)28510-28522
JournalOncotarget
Volume7
Issue number19
DOIs
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

Fingerprint

Genetic Testing
Thyroid Neoplasms
Cell Survival
Receptor Protein-Tyrosine Kinases
RNA Interference
Mitogen-Activated Protein Kinases
Protein Kinases
Small Interfering RNA
Thyroid Gland
Proteins
Phosphotransferases
Cell Proliferation
Cell Line
Neoplasms
Papillary Thyroid cancer
Anaplastic Thyroid Carcinoma

Keywords

  • kinases
  • screening
  • siRNA
  • thyroid carcinoma

Cite this

Cantisani, M. C., Parascandolo, A., Perälä, M., Allocca, C., Fey, V., Sahlberg, N., ... Castellone, M. D. (2016). A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability. Oncotarget, 7(19), 28510-28522. https://doi.org/10.18632/oncotarget.8577
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. / A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability. In: Oncotarget. 2016 ; Vol. 7, No. 19. pp. 28510-28522.
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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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Cantisani, MC, Parascandolo, A, Perälä, M, Allocca, C, Fey, V, Sahlberg, N, Merolla, F, Basolo, F, Laukkanen, MO, Kallioniemi, OP, Santoro, M & Castellone, MD 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

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

In: Oncotarget, Vol. 7, No. 19, 2016, p. 28510-28522.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability

AU - Cantisani, Maria Carmela

AU - Parascandolo, Alessia

AU - Perälä, Merja

AU - Allocca, Chiara

AU - Fey, Vidal

AU - Sahlberg, Niko

AU - Merolla, Francesco

AU - Basolo, Fulvio

AU - Laukkanen, Mikko O.

AU - Kallioniemi, Olli Pekka

AU - Santoro, Massimo

AU - Castellone, Maria Domenica

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - kinases

KW - screening

KW - siRNA

KW - thyroid carcinoma

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DO - 10.18632/oncotarget.8577

M3 - Article

VL - 7

SP - 28510

EP - 28522

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 19

ER -

Cantisani MC, Parascandolo A, Perälä M, Allocca C, Fey V, Sahlberg N et al. A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability. Oncotarget. 2016;7(19):28510-28522. https://doi.org/10.18632/oncotarget.8577