Abstract 2008: CUL7 promotes non-small cell lung cancer cells migration and invasion

Abstract

Abstract Cullin7 (CUL7) is a scaffold protein of the CUL7 E3 ubiquitin ligase containing Fbxw8, Skp1 and ROC1. Germ line mutations of the CUL7 are linked to 3-M syndrome and Yakuts short stature syndrome, both of which are characterized by growth retardation and few bone abnormalities. We have previously shown that CUL7 promotes trophoblast cells migration and invasion. However, the role of CUL7 on cancer invasion and metastasis remains unknown. It has been reported that CUL7 mRNA is overexpressed in non-small cell lung cancer (NSCLC). In this study, we investigated the effects of CUL7 on NSCLC cells migration and invasion. Firstly, we evaluated CUL7 expression on tissue microarray slides by immunohistochemical staining. We found that CUL7 significantly overexpressed in NSCLC and its expression was associated with advanced TNM stage, nodal or bone metastasis and poor overall survival. Next, we determined CUL7, CUL1 and Fbxw8 expression in different NSCLC cell lines by real-time PCR and western blot. Higher level of CUL7 was observed in H1299, H358, H1437, and H1792 cells which derived from metastatic sites compared to H460 and human bronchial epithelial cells (BEAS2B). Knockdown CUL7 expression in NSCLC cells decreased cell motility and invasive ability using wound healing and matrigel invasion assay. Real-time PCR revealed that knockdown of CUL7 significantly decreased expression of CCL2, IL-6 and CXCL16. However, the expression of uPA, MMP-2 and MMP-9 were not changed. Furthermore, Knockdown of CUL7 in NSCLC cells decreased secretion of CCL2, CXCL16 and IL-6. This study indicates that CUL7 may be a potential biomarker as well as a novel therapeutic target in NSCLC progression. Supported by National Natural Sciences Foundation (NSFC) projects (81201669, 81171993 and 81272415); NSFC key project (81130046). Note: This abstract was not presented at the meeting. Citation Format: Qiong Song, Lihui Wang, Yi Lu, Jian Zhang, Jiejun Fu. CUL7 promotes non-small cell lung cancer cells migration and invasion. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2008. doi:10.1158/1538-7445.AM2014-2008