Expression of Hugl-1 is strongly reduced in malignant melanoma.
The human gene Hugl-1 (Llgl/Lgl1) has significant homology to the Drosophila tumor suppressor gene lethal(2)giant larvae (lgl). The lgl gene codes for a cortical cytoskeleton protein, Lgl, that is involved in maintaining cell polarity and epithelial integrity. We speculate that Hugl-1 might play a role in epithelial-mesenchymal transition (EMT) and that loss of Hugl-1 expression plays a role in the development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of Hugl-1 transcription. 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. Reduced Hugl-1 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Functional assays with stable Hugl-1-transfected cell lines revealed that Hugl-1 expression increased cell adhesion and decreased cell migration. Further, downregulation of MMP2 and MMP14 (MT1-MMP) and re-expression of E-cadherin was found in the Hugl-1-expressing cell clones supporting a role of Hugl-1 in EMT. Our studies thus indicate that loss of Hugl-1 expression contributes to melanoma progression.
Kuphal
S
S
Institute of Pathology, University Regensburg, Regensburg, Germany.
Wallner
S
S
Schimanski
C C
CC
Bataille
F
F
Hofer
P
P
Strand
S
S
Strand
D
D
Bosserhoff
A K
AK
D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D003598:Cytoskeletal Proteins; D018450:Disease Progression; D015536:Down-Regulation; D004848:Epithelium / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D053504:Matrix Metalloproteinases, Membrane-Associated; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014162:Transfection
D015820:Cadherins; D003598:Cytoskeletal Proteins; C097906:LLGL1 protein, human; D011506:Proteins; D012333:RNA, Messenger; D012313:RNA; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D020778:Matrix Metalloproteinase 2; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14