Abstract
BackgroundMounting evidence has showed that Tumor-associated calcium signal transducer 2 (Trop2) is upregulated in various kinds of human cancers and plays important roles in tumorigenesis. However, the expression status and functional significance of Trop2 in thyroid cancer are largely unknown.MethodsWe first determined the expression of Trop2 by using RNAseqV2 data sets for thyroid cancer deposited on The Cancer Genome Atlas (TCGA) website. The expression of Trop2 was then confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. Cell invasion and migration were assessed by conducting Transwell and wound healing assays. Furthermore, we explored the underlying mechanisms by using real-time RT-PCR, Western blot, zymography, and luciferase reporter assays.ResultsIn this study, we demonstrated that the expression of Trop2 was significantly elevated in thyroid cancer and that its expression level was correlated with the tumor-node-metastasis (TNM) staging and N classification. Dysregulation of Trop2 altered the invasive capability of thyroid cancer cells. Further mechanistic study revealed that MMP2 expression was upregulated by Trop2. Moreover, we found that the effects of Trop2 were dependent on ERK and JNK pathways. The results from clinical specimens showed that Trop2 expression correlated with MMP2 expression in primary thyroid cancer.ConclusionThe current study suggests that elevated expression of Trop2 may represent an important molecular hallmark that is biologically and clinically relevant to the progression of thyroid cancer.
Highlights
Mounting evidence has showed that Tumor-associated calcium signal transducer 2 (Trop2) is upregulated in various kinds of human cancers and plays important roles in tumorigenesis
trophoblast cell-surface antigen 2 (Trop2) is overexpressed in thyroid cancer To explore the expression of Trop2 in thyroid cancer, we initially investigated the expression of Trop2 in 59 pairs of thyroid tumors and their adjacent nontumorous thyroid tissues using RNAseqV2 data sets for thyroid cancer deposited on The Cancer Genome Atlas (TCGA, https://cancergenome.nih.gov/) website
The results showed that Trop2 expression level was significantly elevated in most thyroid cancer tissues as compared with their respectively adjacent non-tumorous thyroid tissues (Fig. 1a)
Summary
Mounting evidence has showed that Tumor-associated calcium signal transducer 2 (Trop2) is upregulated in various kinds of human cancers and plays important roles in tumorigenesis. The expression status and functional significance of Trop in thyroid cancer are largely unknown. Human tumor-associated calcium signal transducer 2 (TACSTD2), known as trophoblast cell-surface antigen 2 (Trop2), is a type I transmembrane glycoprotein originally identified in human placental trophoblastic tissue [5]. The biological function of Trop is unclear, accumulating evidence has demonstrated that its expression is elevated in various malignant tissues, whereas in human normal tissues relatively low or no Trop expression is observed [8,9,10,11]. Over-expression of Trop has been implicated to correlate with poor prognosis of patients with several kinds of cancers [12, 13]
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