Inhibition of tissue transglutaminase sensitizes TRAIL-resistant lung cancer cells through upregulation of death receptor 5

Frese-Schaper, Manuela; Schardt, Julian A; Sakai, Toshiyuki; Carboni, Giovanni L; Schmid, Ralph A; Frese, Steffen (2010). Inhibition of tissue transglutaminase sensitizes TRAIL-resistant lung cancer cells through upregulation of death receptor 5. FEBS letters, 584(13), pp. 2867-71. Amsterdam: Elsevier 10.1016/j.febslet.2010.04.072

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
UniBE Contributor:	Frese, Manuela, Carboni, Giovanni Luca, Schmid, Ralph, Frese, Steffen R.
ISSN:	0014-5793
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:07
Last Modified:	05 Dec 2022 14:00
Publisher DOI:	10.1016/j.febslet.2010.04.072
PubMed ID:	20450916
Web of Science ID:	000278657200025
URI:	https://boris.unibe.ch/id/eprint/279 (FactScience: 197297)