Abstract
Papillary thyroid cancer (PTC) is one of the endocrine cancers with high clinical and genetic heterogeneity. NOTCH signaling and its downstream NOTCH-Regulated Ankyrin Repeat Protein (NRARP) have been implicated in oncogenesis of many cancers, but the roles in PTCs are less studied. In this study, we show that NRARP is frequently over-expressed in thyroid carcinoma. The over-activation of NRARP is highly and positively correlated with NOTCH genes. Moreover, we find that the expression of NRARP is highly associated with several epithelial mesenchymal transition (EMT) markers and contributes to poor survival outcomes. Therefore, these results indicate that NRARP is an important clinical biomarker in thyroid carcinoma and it promotes EMT induction as well as the progression of PTCs via NOTCH signaling activation.
Highlights
Thyroid carcinoma is the most common type of the endocrine cancers with high clinical and genetic heterogeneity
Previous studies reported that activation of mitogen-activated protein kinase (MAPK) signaling pathway is frequently observed in papillary thyroid carcinoma (PTC) patients
A recent study reported that NOTCH signaling, another cancer related pathway involved in oncogenic transformation [7, 8], is induced by MAPK signaling and promotes tumor growth in PTC [9]
Summary
Thyroid carcinoma is the most common type of the endocrine cancers with high clinical and genetic heterogeneity. Some aggressive and metastatic thyroid cancers can result from poorly differentiated tumor cells. Previous studies reported that activation of mitogen-activated protein kinase (MAPK) signaling pathway is frequently observed in PTC patients. The genetic alterations like BRAF or RAS mutation [3] and RET or NTRK1 fusions [4, 5] can result in the activation of MAPK signaling pathway, and lead to dys-regulation of cell differentiation, cell proliferation and cell survival [6]. A recent study reported that NOTCH signaling, another cancer related pathway involved in oncogenic transformation [7, 8], is induced by MAPK signaling and promotes tumor growth in PTC [9]
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