Poster abstracts
Poster number 74 submitted by Chaojie Wang
RCAN1-4 is a thyroid cancer growth and metastasis suppressor
Chaojie Wang (Ohio State Biochemistry Program), Motoyasu Saji (Department of Internal Medicine), Steven E. Justiniano (Department of Internal Medicine), Adlina Mohd Yusof (Department of Internal Medicine), Xiaoli Zhang (Department of Biomedical Informatics), Matthew Ringel (Department of Internal Medicine)
Abstract:
Metastasis suppressors are key regulators of tumor growth, invasion, and metastases. Loss of metastasis suppressors has been associated with aggressive tumor behaviors and metastatic progression. We previously showed Regulator of Calcineurin 1, isoform 4 (RCAN1-4) was upregulated by the KiSS1 metastatic suppression pathway and could inhibit cell motility when overexpressed in cancer cells. To test the effects of endogenous RCAN1-4 loss on thyroid cancer in vivo, we developed RCAN1-4 knockdown stable cells. Subcutaneous xenograft models demonstrated that RCAN1-4 knockdown promotes tumor growth. Intravenous metastasis models demonstrated that RCAN1-4 loss promotes tumor metastases to the lungs and their subsequent growth. Finally, stable induction of RCAN1-4 expression reduced thyroid cancer cell growth and invasion. Microarray analysis predicted Nuclear Factor, Erythroid 2-Like 3 (NFE2L3) was a pivotal downstream effector of RCAN1-4. NFE2L3 overexpression was shown necessary for RCAN1-4-mediated enhanced growth and invasiveness and NEF2L3 overexpression independently increased cell invasion. In human samples, NFE2L3 was overexpressed in TCGA thyroid cancer samples versus normal tissues and NFE2L3 overexpression was demonstrated in distant metastasis samples from thyroid cancer patients. In conclusion, we provide the first evidence that RCAN1-4 is a growth and metastasis suppressor in vivo and it functions in part through NFE2L3.
Keywords: RCAN1-4, Thyroid Cancer , Metastasis Suppressor