An oncogenic role of Agrin in regulating focal adhesion integrity in hepatocellular carcinoma

• DOI: 10.1038/ncomms7184
• Publication Date: 2015-01-29T10:35:08Z
• Authors: Sayan Chakraborty; Manikandan Lakshm...; Hannah L.F. Swa; Jianxiang Chen; Xiaoqian Zhang; Yan Shan Ong; Li Shen Loo; Semih Can Akıncılar; Jayantha Gunaratne; Vinay Tergaonkar; Kam M. Hui; Wanjin Hong
• Keywords: Agrin

Abstract Hepatocellular carcinoma (HCC) is one of the leading causes cancer-related deaths globally. The identity and role cell surface molecules driving complex biological events to HCC progression are poorly understood, hence representing major lacunae in therapies. Here, combining SILAC quantitative proteomics biochemical approaches, we uncover a critical oncogenic Agrin, which overexpressed secreted HCC. Agrin enhances cellular proliferation, migration signalling. Mechanistically, Agrin’s extracellular matrix sensor activity provides cues regulate Arp2/3-dependent ruffling, invadopodia formation epithelial–mesenchymal transition through sustained focal adhesion integrity that drives liver tumorigenesis. Furthermore, signalling Lrp4-muscle-specific tyrosine kinase (MuSK) forms axis. Importantly, antibodies targeting reduced tumour growth vivo . Together, demonstrate frequently upregulated important for property HCC, an attractive target antibody therapy.