LMO7 as an Unrecognized Factor Promoting Pancreatic Cancer Progression and Metastasis

Abstract

Pancreatic cancer (PC) is one of the most lethal human malignancies without effective treatment. In an effort to discover key genes and molecular pathways underlying PC growth, we have identified LIM domain only 7 (LMO7) as an under-investigated molecule, which highly expresses in primary and metastatic human and mouse PC with the potential of impacting PC tumorigenesis and metastasis. Using genetic methods with siRNA, shRNA, and CRISPR-Cas9, we have successfully generated stable mouse PC cells with LMO7 knockdown or knockout. Using these cells with loss of LMO7 function, we have demonstrated that intrinsic LMO7 defect significantly suppresses PC cell proliferation, anchorage-free colony formation, and mobility in vitro and slows orthotopic PC tumor growth and metastasis in vivo. Mechanistic studies demonstrated that loss of LMO7 function causes PC cell-cycle arrest and apoptosis. These data indicate that LMO7 functions as an independent and unrecognized druggable factor significantly impacting PC growth and metastasis, which could be harnessed for developing a new targeted therapy for PC.

Comprehensive Analysis of Expression, Prognostic Value, and Immune Infiltration for Ubiquitination-Related FBXOs in Pancreatic Ductal Adenocarcinoma

“…In contrast, FBXO20 could facilitate the migration ability of breast cancer cells in a cell-specific manner via modulating Rho-MRTF-SRF signaling ( 14 ). Liu et al verified that the expression levels of FBXO20 mRNA and protein were increased in mouse and human pancreatic cancer tissues ( 16 ). The results of Liu were consistent with our findings in multiple public databases to some extent.…”

“…FBXO20, also known as LIM (Lin11, Isl-1, and Mec-3) domain 7 (LMO7), belongs to PDZ and the LIM domain-containing protein family. It has been reported that LMO7 played a role in the regulation of cell adhesion, mitosis, and cancer metastasis and progression, including breast cancer, lung adenocarcinoma, and pancreatic cancer (13)(14)(15)(16). Clinically, some FBXO family members were closely linked to the overall survival (OS) and disease-free survival (DFS) of patients with breast cancer (17).…”

CXCR3 Expression and Genome-Wide 3′ Splice Site Selection in the TCGA Breast Cancer Cohort

“…CXCR3-A and CXCR3-B are the best studied isoforms and differ in their 3′ splice site on exon 2, which are 245 bp apart. CXCR3-B uses a more proximal 3′ splice site than CXCR3-A, which results in a longer extracellular N-terminus [ 1 , 2 ] ( Figure 1 ). Notably, CXCR3-B uses a more downstream start codon.…”

“…Immune cells have been shown to mainly express CXCR3-A, with low levels of CXCR3-B co-expression [ 2 , 4 ]. In contrast, endothelial cells and pericytes only express CXCR3-B [ 1 , 2 ].…”

New Findings on LMO7 Transcripts, Proteins and Regulatory Regions in Human and Vertebrate Model Organisms and the Intracellular Distribution in Skeletal Muscle Cells

“…Regarding its intracellular distribution, the LMO7 protein can be found in the nucleus, perinuclear region, cytoplasm and/or on cell surface, particularly in cell–cell adhesions (where it can interact with nectin and E-cadherin through afadin and alpha-actinin) and focal adhesions [ 2 , 8 , 9 , 10 ]. Importantly, misregulation of the PDZ–LIM proteins is involved in cancer [ 11 , 12 ].…”