Inhibitor of DNA binding-1 induces mesenchymal features and promotes invasiveness in thyroid tumour cells

Abstract

Characterisation of molecular mechanisms that control tumour invasion is a crucial step for the identification of molecular markers to apply in cancer diagnosis and treatment. In this work, we have investigated the role of Id1 in thyroid tumours. We demonstrate that Id1 participates to tumour progression by powering the invasion capacity of cancer cells. We prove that the overexpression of Id1 in thyroid tumour cells profoundly alters cell morphology and growth, increasing migration and invasion properties of the cells. Analysis in human thyroid tumours reveals that Id1 is expressed in invading cells and its expression is associated with an increased metastatic potential of non-anaplastic tumours. The gene expression study supports these observations demonstrating that Id1 modulates a number of genes known to control invasion, aggressiveness and pharmacological resistance in different type of human tumours. Finally, we demonstrate that the pro-invasive effect of Id1 is accompanied by the acquisition of mesenchymal features in thyroid tumour cells. This suggests that the trans-differentiation towards a more immature condition is the mechanism through which Id1 promotes thyroid tumour metastatic spreading. This study identifies Id1 as part of the pro-metastatic programme of thyroid cancer and suggests its possible utilisation as a prognostic marker.