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Inhibition of tissue transglutaminase sensitizes TRAIL‐resistant lung cancer cells through upregulation of death receptor 5
Author(s) -
Frese-Schaper Manuela,
Schardt Julian A.,
Sakai Toshiyuki,
Carboni Giovanni L.,
Schmid Ralph A.,
Frese Steffen
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.04.072
Subject(s) - tissue transglutaminase , downregulation and upregulation , apoptosis , cancer research , tumor necrosis factor alpha , programmed cell death , receptor , sensitization , biology , lung cancer , cancer cell , chemistry , microbiology and biotechnology , cancer , immunology , medicine , pathology , gene , enzyme , biochemistry , genetics
Tissue transglutaminase (TG2) is implicated in cellular processes such as apoptosis and cell migration. Its acyl transferase activity cross‐links certain proteins, among them transcription factors were described. We show here that the TG2 inhibitor KCC009 reversed resistance to tumor necrosis factor‐related apoptosis‐inducing factor (TRAIL) in lung cancer cells. Sensitization required upregulation of death receptor 5 (DR5) but not of death receptor 4. Upregulation of DR5 involved the first intron of the DR5 gene albeit it was independent from p53 and nuclear factor kappa B. In conclusion, inhibition of tissue transglutaminase provides an interesting strategy for sensitization to TRAIL‐induced apoptosis in p53‐deficient lung cancer cells.