FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo.

Credendino, Sara C; De Menna, Marta; Cantone, Irene; Moccia, Carmen; Esposito, Matteo; Di Guida, Luigi; De Felice, Mario; De Vita, Gabriella (2021). FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo. International journal of molecular sciences, 22(14) MDPI 10.3390/ijms22147666

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Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie

UniBE Contributor:

De Menna, Marta

ISSN:

1422-0067

Publisher:

MDPI

Language:

English

Submitter:

Khiem Duong

Date Deposited:

12 Jan 2022 11:39

Last Modified:

12 Jan 2022 11:39

Publisher DOI:

10.3390/ijms22147666

PubMed ID:

34299284

Uncontrolled Keywords:

FOXE1 TAMs chemokines tumour microenvironment

BORIS DOI:

10.48350/162236

URI:

https://boris.unibe.ch/id/eprint/162236

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