Abstract 4108: NKX6.1 suppresses cancer invasion and epithelial-mesenchymal transition in cervical cancer

Abstract

Abstract Cervical cancer is a common women malignancy worldwide. Recent reports emphasize inactivation of tumor suppressor genes are due to promoter hypermethylation in cervical cancer. Our previous study from methylation array has shown NK6 homeobox 1 (NKX6.1) is hypermethylated and downregulated in cervical cancer cell lines and clinical samples. Nkx6.1 contains a homeobox domain and functions as a transcription factor that regulates insulin-secreting β cell differentiation and neuronal fate determination. However, the biological function of NKX6.1 in cervical cancer remains elusive. Overexpression of NKX6.1 suppressed the transformation and invasive ability of HeLa and CaSki cells in vitro as well as decreased tumor formation and metastatic property in vivo. Conversely, knockdown of NKX6.1 strongly enhanced the transformation and invasiveness of SiHa cells. Epithelial-mesenchymal transition (EMT) has been shown to play a key role in the progression of uterine cervix carcinoma in situ (CIS) to invasive squamous cell carcinoma (SCC). NKX6.1 suppresses cancer invasiveness through coordinately increasing E-cadherin and decreasing Vimentin. Moreover, we demonstrated E-cadherin and vimentin were direct targets of NKX6.1 by luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation quantitative polymerase chain reaction (Chip-qPCR) assay. Collectively, our data demonstrate NKX6.1 acts a tumor suppressor, and inhibits tumor invasion and metastasis by suppressing Epithelial-mesenchymal transition (EMT) in cervical cancer. These data imply that modulation of NKX6.1 expression may be a novel therapeutic option for treatment of cervical cancer. Citation Format: Hsin-Jung Li, Pei-Ning Yu, Yu-Lueng Shih, Ya-Wen Lin. NKX6.1 suppresses cancer invasion and epithelial-mesenchymal transition in cervical cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4108. doi:10.1158/1538-7445.AM2015-4108