Disease relevance of TM4SF1

• The L6 antigen is mainly expressed in lung, breast, colon, ovarian carcinomas, and healthy epithelial tissue in humans [1].
• Tumor-associated antigen L6 and the invasion of human lung cancer cells [2].
• Thus, TAL6 appears to be involved in cancer invasion and metastasis [2].
• Immunohistology of skin biopsies displayed a strong expression of L6 in follicular epidermis and epidermolytic lesions of autoimmune bullous dermatoses (bullous pemphigoid, pemphigus vulgaris), but not in normal interfollicular epidermis [3].
• The tumor-associated antigen L6 (TAL6), a distant member of the TM4SF, is expressed on most epithelial cell carcinomas and is a target for antibody-mediated therapy [2].

High impact information on TM4SF1

• The L6 cell surface antigen, which is highly expressed on lung, breast, colon, and ovarian carcinomas, has attracted attention as a therapeutic target for murine monoclonal antibodies and their humanized counterparts [4].
• COS cells transfected with this cDNA direct the expression of an approximately 24-kDa surface protein that reacts with the two anti-L6 monoclonal antibodies available [4].
• The predicted L6 peptide sequence is 202 amino acids long and contains three predicted NH2-terminal hydrophobic transmembrane regions, which are followed by a hydrophilic region containing two potential N-linked glycosylation sites and a COOH-terminal hydrophobic transmembrane region [4].
• The L6 antigen is related to a number of cell surface proteins with similar predicted membrane topology that have been implicated in cell growth [4].
• A kinetic study of splenic reconstitution was performed in mice that received hCTLA4-Ig and showed that mature splenic localized CD8+ T-cell repopulation was not significantly different in recipients of hCTLA4-Ig compared with hL6, despite the significant increase in actuarial survival rate in that experiment [5].

Biological context of TM4SF1

• This cDNA contains one long open reading frame, which encodes a 220-amino acid polypeptide that is 78% homologous to H-L6 [6].
• After artificial wounding of confluent HaCaT cultures, anti-L6 antibody strongly impaired cell migration velocity and migratory reepithelization of the defect, indicating L6 involvement in keratinocyte migration [3].
• In contrast to normal keratinocytes, HaCaT cells showed constitutive L6 expression, indicating a constitutively active phenotype [3].
• The Philadelphia (Ph') chromosome in chronic myelogenous leukemia (CML) results in fusion of the bcr gene and c-abl oncogene, which transcribes into two types of chimeric bcr/abl mRNAs: the L-6 junction and the K-28 junction [7].
• The L6 rust resistance gene from flax generates at least four transcript classes by alternative splicing of the third intron [8].

Anatomical context of TM4SF1

• In comparison with 17 other human tissues and cell types by microarray, large adipocytes displayed by far the highest SAA and TM4SF1 expression [9].
• We have previously demonstrated that the murine L6 mAb recognizes a protein epitope expressed on human tumor-derived cell lines [6].
• These findings suggest that L6 is an important activation-dependent regulator of keratinocyte function and epidermal tissue regeneration [3].
• Amount of expression of the tumor-associated antigen L6 gene and transmembrane 4 superfamily member 5 gene in gastric cancers and gastric mucosa [10].
• Moreover, binding of all four analogues to the IGFBPs secreted by L6 myoblasts and H35B hepatoma cells was greatly decreased compared with the parent IGF [11].

Associations of TM4SF1 with chemical compounds

• A second transporter, the insulin-sensitive glucose transporter, was also observed to be expressed in the L6 cells [12].
• Interestingly, the L6 ribosomal protein from L. braziliensis contains a specific region of 14 aa and a tyrosine kinase motif, which is absent in human and C. elegans L6 protein [13].
• RESULTS: One up-regulated gene, glycoprotein hormone alpha-subunit, and two down-regulated genes coding membrane proteins, human folate receptor and tumor-associated antigen L6, were identified in KB/cDDP cells [14].

Other interactions of TM4SF1

• The A15, L6, and S5.7(TAPA1) proteins are members of the transmembrane 4 superfamily (TM4SF) [1].
• From these observations, we generated testable hypotheses regarding several genes including DKFZP, RAP-1, ribosomal protein S6, and TM4SF1 [15].
• The sequence -Y-X-C-COOH, bound in vitro by SITAC, is present in the member of the tetraspanin superfamily, the L6 antigen [16].
• CD13 (aminopeptidase N) can associate with tumor-associated antigen L6 and enhance the motility of human lung cancer cells [17].
• PURPOSE: The aim of this study was to compare carcinoembryonic antigen levels with detection of messenger ribonucleic acid coding for the tumor-associated antigen L6 in patients with colorectal cancer [18].

Analytical, diagnostic and therapeutic context of TM4SF1

• The present findings should make it possible to further study the role of the L6-defined antigen in normal and neoplastic cells and to construct animal models for development of improved agents for active and passive cancer immunotherapy [4].
• We recently reported that the expression of tumor-associated antigen L6 (TAL6) promoted the invasiveness of lung cancer cells and was inversely correlated with disease-free survival of squamous lung carcinoma patients [17].
• CD13 was shown by coimmunoprecipitation to associate in vitro with TAL6 on several cancer cell lines and to associate in vivo by antibody-mediated copatching immunofluorescence [17].
• Only in Dukes D tumors did the enzyme-linked immunosorbent assay for carcinoembryonic antigen exhibit the same sensitivity as reverse-transcription polymerase chain reaction for L6 messenger ribonucleic acid [18].
• The sequence analysis of the L. braziliensis L6 gene shows a single open reading frame, which codes for a protein of 192 amino acids (aa) with a hypothetical molecular mass of 20.9 kDa [13].

References