Disease relevance of LRIG1

• Their structural relative in mammals, LRIG1, is a transmembrane protein whose inactivation in rodents promotes skin hyperplasia, suggesting involvement in EGFR regulation [1].
• LRIG1 and epidermal growth factor receptor in renal cell carcinoma: a quantitative RT--PCR and immunohistochemical analysis [2].
• We propose that a common, but hitherto unrecognised, breast cancer linked gene is located within an amplicon containing the LRIG1 locus at 3p14.3 [3].
• LRIG-1 provides a novel prognostic predictor in squamous cell carcinoma of the skin: immunohistochemical analysis for 38 cases [4].
• Expression of EGFR and LRIG-1 in human trigeminal neurinoma [5].

High impact information on LRIG1

• We report upregulation of LRIG1 transcript and protein upon EGF stimulation, and physical association of the encoded protein with the four EGFR orthologs of mammals [1].
• We conclude that LRIG1 evolved in mammals as a feedback negative attenuator of signaling by receptor tyrosine kinases [1].
• Upregulation of LRIG1 is followed by enhanced ubiquitylation and degradation of EGFR [1].
• Down-regulation of Lrig1 using siRNA increased cell-surface EGF receptor levels, enhanced activation of downstream pathways, and stimulated proliferation [6].
• Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence [6].

Chemical compound and disease context of LRIG1

• The expression of epidermal growth factor receptor (EGFR) and leucine-rich repeats and immunoglobulin-like domain 1 (LRIG-1) in human trigeminal neurinoma was investigated and their effect on the origination and development of trigeminal neurinoma, and the relationship between them was studied [5].

Biological context of LRIG1

• MATERIALS AND METHODS The plasmid pLRIG1-green fluorescence protein (GFP) was transfected into BIU87 bladder cancer cells by Lipofectamine2000 (Invitrogen, Groningen, the Netherlands), and the cells that expressed LRIG1 stably were screened out by G418 [7].
• Genetic studies have implicated a tumour suppressor gene on chromosome arm 3p and we have proposed LRIG1 at 3p14 as a candidate tumour suppressor [3].
• The LRIG1 protein can inhibit the growth of tumors of glial cells and the down-regulation of the LRIG1 gene may be involved in the development and progression of the tumor [8].
• We tested an expressed sequence tag, two predicted genes, one novel gene and LRIG1, a gene located more than 200 kb apart from the breakpoint on chromosome 3 [9].
• A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity [10].

Anatomical context of LRIG1

• The ratio between EGFR and LRIG1 was more than 2.5-fold higher in the eight tumours compared with matched uninvolved kidney cortex and was at least two-fold higher than the mean normal ratio in 21 of 31 samples analysed [2].
• LRIG1, a candidate tumour-suppressor gene in human bladder cancer cell line BIU87 [7].
• Immunoblotting demonstrated LRIG1 protein in tissue lysates from normal human prostate, mammary epithelial cells, ileum, stomach, lung, and cerebral cortex [11].
• Immunoblotting analysis of cell-surface-biotinylated lysates and confocal microscopy revealed that LRIG1 was localized to the cell surface in ZR-75 cells expressing endogenous LRIG1 and in COS-7 cells expressing a synthetic LRIG1-GFP fusion protein [11].
• Overexpression of Lrig1 decreased keratinocyte proliferation but did not affect the proportion of stem and transit-amplifying cells, as judged by clonal growth characteristics [6].

Associations of LRIG1 with chemical compounds

• The LRIG2 protein was predicted to have the same domain organization as LRIG1 with a signal peptide, an extracellular part containing15 leucine-rich repeats and three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail [12].
• LRIG1 migrated in denaturing polyacrylamide gel electrophoresis under reducing conditions as two species with apparent molecular weights of 143 kDa and 134 kDa, and as two fragments corresponding to an N-terminal 111-kDa species and a C-terminal 32-kDa species [11].
• Integrin engagement also inhibited increases in gammaH2AX in BLM-treated cells transfected with Lig1 siRNA [13].
• LRIG1 opposes Met synergy with the ErbB2/Her2 receptor tyrosine kinase in driving cellular invasion [14].

Regulatory relationships of LRIG1

• It was suggested that LRIG-1 might inhibit the malignant differentiation and proliferation of the trigeminal neurinoma possibly by the negative feedback loop of EGFR [5].

Other interactions of LRIG1

• In all, 31 renal cell carcinomas (RCCs) were examined for expression of the potential tumour suppressor LRIG1 (formerly Lig-1) and the epidermal growth factor receptor (EGFR) [2].
• Leucine-rich repeats and immunoglobulin-like domains-1 (LRIG1) is a transmembrane protein with an ectodomain containing 15 leucine-rich repeats (LRRs) homologous to mammalian decorin and the Drosophila kekkon1 gene [10].

Analytical, diagnostic and therapeutic context of LRIG1

• The changes in LRIG1 and epidermal growth factor receptor (EGFR) protein levels were measured by Western blot; growth curves were estimated by the tetrazolium (MTT) assay; then cell-cell adhesion, cell-matrix adhesion and cell invasion assays were used to measure proliferation, adhesion and invasion in LGIR1-transfected and control cells [7].
• METHODS: In the present report we analysed the LRIG1 gene by fluorescence in situ hybridisation (FISH), LRIG1 mRNA by quantitative RT-PCR, and LRIG1 protein by western blot analysis [3].
• We have searched for additional members of the LRIG family and by molecular cloning identified human LRIG3 and its mouse ortholog Lrig3 [15].
• LRIG-1 expression in 38 cases of cutaneous SCC patients was examined by immunohistochemistry [4].

References