The role of LIM domain and LIM domain binding proteins in human head and neck carcinoma

Abstract

Head and neck squamous cell carcinoma is a frequent and serious malignancy that accounts for more than 300,000 deaths world wide each year, the majority of which are the result of local invasion and lymph node metastasis. LIM-only protein 4 (LMO4) and LIM-domain binding protein 1 (LDB1), transcriptional adaptors that have important roles in normal epithelial cell differentiation, have also been associated with increased lymph node metastasis and decreased differentiation in carcinomas of the breast and of the head and neck. Here within, LMO4 and LDB1, in addition to single-stranded-binding proteins (SSBPs) are involved in regulating invasion, and provides an explanation for why LMO4 and LDB1 have concordant levels of expression in this disease. This work directly shows that VU-SCC-1729 cells can invade cellular monolayers and that loss of LDB1 in these cells not only reduces invasion, but also plays an unexpected role in the reduction of proliferation. A loss of LDB1 in VU-SCC-1729 cells also resulted in reduced tumor volume and vascularization in a xenograft tumor model. Genome-wide DNA occupancy studies evaluated LDB1 and SSBP2 binding patterns in head and neck cancer cells. Together, these data suggest that LMO4, LDB1, and SSBPs may have a collective role in regulating processes critical for progression of head and neck carcinoma including invasion, proliferation, and angiogenesis.