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Updated: Mar 22, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability
Maria Carmela Cantisani1, Alessia Parascandolo2, Merja Perälä3,4
1IRCCS SDN, Naples, Italy.
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.
Insights
Researchers screened thyroid cancer cells for essential kinases, identifying 14 novel targets. These kinases are crucial for cancer cell survival but not normal cells, offering potential new therapeutic strategies for thyroid cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Protein kinases like RET and BRAF are key in thyroid cancer development.
- Identifying novel kinases is crucial for developing targeted therapies.
- Thyroid carcinoma exhibits complex molecular alterations driving its progression.
Purpose of the Study:
- To identify novel kinases essential for thyroid carcinoma cell viability and proliferation.
- To screen the human kinome for potential therapeutic targets in thyroid cancer.
- To assess the specificity of identified kinases in cancer versus normal thyroid cells.
Main Methods:
- RNA interference (siRNA) screening was performed on the TPC1 papillary thyroid cancer cell line.
- A library of synthetic siRNAs targeting the human kinome was utilized.
- Cell viability and proliferation were measured after silencing identified kinases.
Main Results:
- 14 kinases were identified whose silencing significantly reduced thyroid cancer cell viability and proliferation.
- These kinases showed activity across various thyroid cancer subtypes, including papillary and anaplastic carcinomas with different mutations (RET, BRAF, RAS).
- Silencing of these kinases did not significantly impact normal thyroid cells (NTHY), indicating cancer-specific effects.
Conclusions:
- The identified kinases represent potential novel, druggable targets for thyroid cancer therapy.
- The specificity for cancer cells suggests a favorable therapeutic window.
- Further exploration of these EPH receptor, SRC, and MAPK family members is warranted for drug development.
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