Abstract 2488: Functional characterization of nuclear TYRO3 in colorectal cancer

Colorectal cancer is one of most common death-related cancers worldwide. Aberrant expression of oncogenes is regarded as a predominant factor in colorectal cancer development. TYRO3 belongs to TAM (TYRO3, AXL, and MER) family, which is a subfamily of receptor tyrosine kinases. Our previous study discovered TYRO3, an oncogene overexpressed in colorectal cancer, promotes cell proliferation, metastasis, and tumor progression. Herein, we further identified that TYRO3 is present in nucleus of colon cancer cells using immunofluorescence staining in conjunction with confocal microscopy. By staining with three different antibodies recognizing N-terminal, central region, and C-terminal of TYRO3, respectively, we identified that central and C-terminal of TYRO3 is the fragment to be translocated to the nucleus. Transfection of exogenous Myc-TYRO3-GFP fusion protein further confirmed this finding. By bioinformatic tool prediction, we found there is a nuclear localization signal (NLS) and a nuclear export signal (NES) in TYRO3. To evaluate the function of nuclear TYRO3, we mutated NLS of TYRO3 and performed several functional studies. Results of immunofluorescent staining showed that after NLS mutation, TYRO3 cannot be translocated to nucleus, which was accompanied by distorted morphology. Furthermore, cancer cells transfected with NLS-mutated TYRO3 increased activated caspase-3 and number of apoptotic cells, suggesting nuclear localization of TYRO3 is essential for cell survival. Clinical data further support that levels of nuclear TYRO3 are a poor prognostic marker that is positively associated with colon cancer treatment failure and malignancy. These data support that nuclear TYRO3 is important for colon cancer cell survival and is a valuable biomarker for prognosis. Citation Format: Shaw-Jenq Tsai, Chun-Wei Chien, Sih-Yu Chen, Shao-Chieh Lin, Bo-Wen Lin, Jenq-Chang Lee. Functional characterization of nuclear TYRO3 in colorectal cancer [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 2488.