LIM-Only Protein 4 (LMO4) and LIM Domain Binding Protein 1 (LDB1) Promote Growth and Metastasis of Human Head and Neck Cancer (LMO4 and LDB1 in Head and Neck Cancer)

Abstract

Squamous cell carcinoma of the head and neck (HNSCC) accounts for more than 300,000 deaths worldwide per year as a consequence of tumor cell invasion of adjacent structures or metastasis. LIM-only protein 4 (LMO4) and LIM-domain binding protein 1 (LDB1), two directly interacting transcriptional adaptors that have important roles in normal epithelial cell differentiation, have been associated with increased metastasis, decreased differentiation, and shortened survival in carcinoma of the breast. Here, we implicate two LDB1-binding proteins, single-stranded binding protein 2 (SSBP2) and 3 (SSBP3), in controlling LMO4 and LDB1 protein abundance in HNSCC and in regulating specific tumor cell functions in this disease. First, we found that the relative abundance of LMO4, LDB1, and the two SSBPs correlated very significantly in a panel of human HNSCC cell lines. Second, expression of these proteins in tumor primaries and lymph nodes involved by metastasis were concordant in 3 of 3 sets of tissue. Third, using a Matrigel invasion and organotypic reconstruct assay, CRISPR/Cas9-mediated deletion of LDB1 in the VU-SCC-1729 cell line, which is highly invasive of basement membrane and cellular monolayers, reduced tumor cell invasiveness and migration, as well as proliferation on tissue culture plastic. Finally, inactivation of the LDB1 gene in these cells decreased growth and vascularization of xenografted human tumor cells in vivo. These data show that LMO4, LDB1, and SSBP2 and/or SSBP3 regulate metastasis, proliferation, and angiogenesis in HNSCC and provide the first evidence that SSBPs control LMO4 and LDB1 protein abundance in a cancer context.

Genome Editing: A New Horizon for Oral and Craniofacial Research

“…As summarized in the Appendix Table, CRISPR/Cas9 has been used to knock out several genes in several HNC cell lines. Those attempts confirm the involvements of fibronectin and LDB1 for cancer cell and invasiveness (Wang et al 2015; Simonik et al 2016) and identify novel therapeutic targets such as p75NTR and MUL1-HSPA5 axis (Huang et al 2017; Kim et al 2018). However, CRISPR may provide greater breakthroughs in treating HNC.…”

Research and Clinical Significance of the Differentially Expressed Genes TP63 and LMO4 in Human Immunodeficiency Virus-related Penile Squamous Cell Carcinoma

“…Deletion of LMO4 impairs Ldb1 and SLK recruitment in migratory cells [24]. LMO4 is closely related to the occurrence of many malignant tumors, such as pancreatic cancer, non-small cell lung cancer, and head and neck cancer [27,28], and can affect the differentiation of T cells, leading to acute leukemia [29].…”

<p>Circ_0058124 Aggravates the Progression of Papillary Thyroid Carcinoma by Activating LMO4 Expression via Targeting miR-370-3p</p>

“…LMO4 functioned as an oncogene in diverse cancers, and high expression of LMO4 was linked to poor prognosis and low survival. 29 , 30 In mechanism, LMO4 interacted with proteins involved, among else, in tumorigenesis, such as P53. 31 Besides, a previous study demonstrated that LMO4 was targeted by miR-139-5p, and circRNA-BACH2 facilitated PTC deterioration by activating the expression of LMO4 by targeting miR-139-5p.…”