Disease relevance of LLGL1

• Our studies thus indicate that loss of Hugl-1 expression contributes to melanoma progression [1].
• Thus, we evaluated tumour tissues from 94 patients undergoing surgery for colorectal cancer (CRC) for loss of Hugl-1 transcription and compared our findings with the clinical data from each of these patients [2].
• Reduced Hugl-1 expression during the adenoma-carcinoma sequence occurring as early as in colorectal adenomas was detected by both immunohistochemical and reverse transcription-polymerase chain reaction analysis [2].
• We found that Hugl-1 was lost in 75% of tumour samples and these losses were associated with advanced stage and particularly with lymph node metastases [2].

High impact information on LLGL1

• We show that an interaction between CD46 and DLG4 is important for polarization in epithelial cells [3].
• We found that Hugl-1 was downregulated or lost in all cell lines and in most of the tumor samples analysed, and that these losses were associated with advanced stage of the disease [1].
• Functional assays with stable Hugl-1-transfected cell lines revealed that Hugl-1 expression increased cell adhesion and decreased cell migration [1].
• Our studies thus indicate that downregulation of Hugl-1 contributes to CRC progression [2].
• The human gene, human giant larvae (Hugl-1/Llg1/Lgl1) has significant homology to the Drosophila tumour suppressor gene lethal(2)giant larvae (lgl) [2].

Biological context of LLGL1

• Sequence analysis of the hugl cDNA demonstrates a long open reading frame, which has the potential to encode a protein of 1057 amino acids with a predicted molecular weight of 115 kDaltons (kD) [4].
• The hugl cDNA detects a locus spanning at least 25 kilobases (kb) in human chromosome band 17p11.2-12, which is centromeric to the p53 gene and recognizes a 4.5 kb RNA transcript [4].
• The FLII gene lies adjacent to LLGL, the human homologue of the D. melanogaster tumor suppressor gene lethal(2) giant larvae [5].
• Overlapping gene structure of human VLCAD and DLG4 [6].
• Interestingly, VLCAD and DLG4 genes do not overlap in the mouse or Drosophila genomes [6].

Anatomical context of LLGL1

• DLG4 was found to be expressed in normal human cells, including cervical keratinocytes, but only to a limited extent in both HPV-positive and HPV-negative cervical cancer cell lines [7].

Associations of LLGL1 with chemical compounds

• Similar to the Drosophila protein, HUGL is part of a cytoskeletal network and, is associated with nonmuscle myosin II heavy chain and a kinase that specifically phosphorylates HUGL at serine residues [4].

Analytical, diagnostic and therapeutic context of LLGL1

• Reduced Hugl-1 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) analysis [1].
• Using radiation-hybrid mapping panels, we mapped the DLG4 locus to 17p13.1, a region associated with several diseases, the phenotypes of which are consistent with loss of PSD95 function [8].

References