Abstract 1058: CRLF1 promotes proliferation and metastasis in papillary thyroid carcinoma via activating MAPK/ERK and PI3K/AKT pathway

Abstract

Abstract Papillary thyroid cancer (PTC) is the most common cancer in endocrine system which accounts for the majority component of thyroid cancer during the past decades. PTCs usually are indolent and curable with 5-year survival rate over 95%. However, some of PTCs will dedifferentiate and become aggressive with a poor prognosis. Current established biomarkers may not fully explain the mechanisms of the development of PTC. Therefore, it is still urgent to find novel biomarkers of PTC to better predict patients' prognosis and lead to the personalized therapies for PTC patients. By analyzing The Cancer Genome Altas (TCGA) database, we identified Cytokine Receptor Like Factor-1(CRLF1) as a potential oncogene. We identified CRLF1 is highly expressed in papillary thyroid carcinoma (PTC) compared with normal thyroid tissues both at mRNA and protein level. High CRLF1 level was associated with aggressive clinicopathological features and worse disease-free survival rate. By loss-of-function and gain-of-function assays, we found that CRLF1 not only boosts capacity of cell migration and invasion in vitro, but promotes tumor growth both in vitro and in vivo. Besides, CRLF1 can induce epithelial-mesenchymal transitions. Overexpressing CRLF1 could activate ERK1/2 and AKT pathways. The oncogenic effects induced by CRLF1 were suppressed by treating the cells with the MEK inhibitor U0126 or the AKT inhibitor MK-2206. These results suggest an oncogenic role CRLF1 plays in PTC tumorigenesis by regulating MAPK/ERK and PI3K/AKT signaling pathways. These results suggest that CRLF1 is a potential biomarker in PTC patients and it may be a valuable therapeutic target for PTC in the future. Citation Format: QIAN ZHONG, Shitong Yu, Xiaoming Huang, Musheng Zeng. CRLF1 promotes proliferation and metastasis in papillary thyroid carcinoma via activating MAPK/ERK and PI3K/AKT pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1058.