The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1

Cell Death & Disease
Cristina GalloAlessia Ciarrocchi

Abstract

Aberrant re-activation of transcription factors occurs frequently in cancer. Recently, we found the basic helix-loop-helix transcription factors DEC1 and DEC2 significantly up-regulated in a model of highly aggressive thyroid cancer, raising the hypothesis that these factors might be part of the program driving progression of these tumors. Here, we investigated for the first time the function of DEC1 and DEC2 in thyroid cancer. Using both gain- and loss-of-function approaches, we showed that DEC1 more than DEC2 sustains progression of thyroid cancer by promoting cell growth and invasiveness. We demonstrated that DEC1 controls NOTCH1 expression and that the interplay with the NOTCH pathway is relevant for DEC1 function in thyroid cancer. We confirmed this observation in vivo showing that DEC1 expression is a specific feature of tumor cells, that this transcription factor is significantly over-expressed in all major thyroid cancer histotypes and that its expression correlated with NOTCH1 in these tumors. Finally, we performed RNA-sequencing to define the DEC1-associated gene expression profile in thyroid cancer cells and we discovered that DEC1 drives the expression of many cell cycle-related genes, uncovering a potential new fun...Continue Reading

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Citations

Jun 25, 2020·Genes & Cancer·Zsofia KissParamita M Ghosh
Aug 14, 2019·Nature Reviews. Endocrinology·Keisuke IkegamiTakashi Yoshimura
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Feb 6, 2022·Journal of Cellular and Molecular Medicine·Yanfei JiaYunshan Wang

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Datasets Mentioned

BETA
E-MTAB-6394

Methods Mentioned

BETA
transfection
RNA-Seq

Software Mentioned

Cufflink
ArrayExpress
String
- Pad Prism
Graph
R

Related Concepts