2005
DOI: 10.4161/cbt.4.4.1623
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Aberrant laminin beta-3 isoforms downstream of EWS-ETS fusion genes in ewing family tumors

Abstract: Ewing family tumors (EFTs) are associated with a chromosomal translocation resulting in a fusion of the amino-terminus of EWS with the DNA-binding domain of an ETS transcription factor. Although previous reports suggested that these chimeric proteins would act as aberrant transcription factors, their downstream targets have not been fully elucidated. To identify downstream targets of these EWS-ETS fusion proteins, we introduced EWS-ETS fusion constructs into a human fibrosarcoma cell line, HT-1080, by retrovir… Show more

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Cited by 5 publications
(3 citation statements)
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“…The fact that the overexpressed h3 chain was not found to assemble into a LN5 heterotrimer and that the overexpressing cells developed higher tumor growth capacity after injection in severe combined immunodeficient mice (35) suggests that a specific sequence within the free h3 chain may become available and responsible for cellular interactions and signal transduction. This is further strengthened by a study showing that the up-regulation of a NH 2 terminus-truncated h3 isoform in Ewing family tumors may favor the observed oncogenic phenotype (36). Together, these results suggest that the MMP7 cleavage of the h3 chain may allow a partial dissociation of the LN5 heterotrimer followed by a possible release/ exposure of an active fragment within the h3 subunit.…”
Section: Discussionmentioning
confidence: 52%
“…The fact that the overexpressed h3 chain was not found to assemble into a LN5 heterotrimer and that the overexpressing cells developed higher tumor growth capacity after injection in severe combined immunodeficient mice (35) suggests that a specific sequence within the free h3 chain may become available and responsible for cellular interactions and signal transduction. This is further strengthened by a study showing that the up-regulation of a NH 2 terminus-truncated h3 isoform in Ewing family tumors may favor the observed oncogenic phenotype (36). Together, these results suggest that the MMP7 cleavage of the h3 chain may allow a partial dissociation of the LN5 heterotrimer followed by a possible release/ exposure of an active fragment within the h3 subunit.…”
Section: Discussionmentioning
confidence: 52%
“…Although the chimeric transcript EWSR1/ERG is able to interfere with different cellular pathways, for example, together with other EWS partners, it can suppress TGF-beta R activity [29]. Several ECM molecules are modulated by EWS/ERG, such as collagen COL11A2 [30], and laminin beta3 [31]. This fusion transcript can also be present in other peripheral primitive neuroectodermal tumor (pPNET) [32] and in desmoplastic small round cell tumor (DSRCT) [33].…”
Section: Ews Translocation Partners In Cancermentioning
confidence: 99%
“…The oncogenic effect of EWS-ETS fusion transcripts, may be partly mediated by upregulation of LAMB3 expression, a gene encoding the β 3 chain of laminin-5. Laminin-5 is frequently found to be strongly expressed in the cytoplasm of invading cancer cells, suggesting its role at the invasive front of colorectal, gastric, pancreatic, and breast tumors, alongside various others [ 33 ]. Many malignancies, experience loss of cell cycle control during multistage progression.…”
Section: Introductionmentioning
confidence: 99%