Poster abstracts
Poster number 66 submitted by Chaojie Wang
RCAN1-4 Regulates Thyroid Cancer Growth and Metastasis
Chaojie Wang (Ohio State Biochemistry Program), Saji Moto (Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine), Steven E Justiniano (Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine), Adlina Mohd Yusof (Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine), Matthew D Ringel (Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine)
Abstract:
Metastatic progression is the main cause of thyroid cancer deaths. Metastasis suppressors are key regulators of tumor invasion and metastases. Loss of metastasis suppressors has been associated with aggressive tumor behaviors and metastatic spread. We previously showed that Regulator of Calcineurin 1, isoform 4 (RCAN1-4) was upregulated by a metastatic suppression pathway and could inhibit cell motility when overexpressed in thyroid cancer cells. Here, we hypothesized RCAN1-4 was a metastasis suppressor in vivo. Using novel RCAN1-4 knockdown stable cells, we showed that knocking down RCAN1-4 in cancer cells promoted cell invasion without affecting cell proliferation. Subcutaneous tumor models demonstrated that RCAN1-4 knockdown in tumor cells increased tumor growth rate and tumor volumes. Metastasis models showed that RCAN1-4 knockdown promoted tumor metastases to the lungs. Microarray analysis discovered Nuclear Factor, Erythroid 2-Like 3 (NFE2L3) was a pivotal downstream effector of RCAN1-4 in regulating tumor metastasis. TCGA thyroid cohort data also demonstrated that NFE2L3 expression was significantly higher in the tumor samples compared with normal tissues. In conclusion, we provided the first evidence that RCAN1-4 was a tumor metastasis suppressor in thyroid cancer cells in vivo.
Keywords: RCAN1-4, Thyroid Cancer, Metastasis