Journal Article

DKFZ-2023-01457

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Transglutaminase 2 is associated with adverse colorectal cancer survival and represents a therapeutic target.

Malkomes, P.DKFZ* ; Lunger, I. ; Oppermann, E. ; Lorenz, J. ; Faqar-Uz-Zaman, S. F. ; Han, J. ; Bothur, S. ; Ziegler, P. ; Bankov, K. ; Wild, P. ; Bechstein, W. O. ; Rieger, M. A.DKFZ*

2023
Nature Publ. Group New York, NY

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Please use a persistent id in citations: doi:10.1038/s41417-023-00641-y

Abstract: Molecular markers for predicting prognosis of colorectal cancer (CRC) patients are urgently needed for effective disease management. We reported previously that the multifunctional enzyme Transglutaminase 2 (TGM2) is essential for CRC cell survival by inactivation of the tumor suppressor p53. Based on these data, we determined the clinical relevance of TGM2 expression and explored its potential as prognostic marker and therapeutic target in CRC. We profiled TGM2 protein expression in tumor samples of 279 clinically characterized CRC patients using immunohistochemical staining. TGM2 expression was upregulated in matched tumor samples in comparison to normal tissue. A strong TGM2 expression was associated with advanced tumor stages and predicted worse prognosis regarding progression-free and overall-survival, even at early stages. Inhibition of TGM2 in CRC cell lines by the inhibitors LDN27219 and Tyrphostin resulted in a strong reduction of cancer cell proliferation and tumorsphere formation in vitro by induction of p53-mediated apoptosis. Primary patient-derived tumorsphere formation was significantly reduced by inhibition of TGM2. Treatment of mice with TGM2 inhibitors exhibited a significant deceleration of tumor progression. Our data indicate that high TGM2 expression in CRC is associated with worse prognosis and may serve as a therapeutic target in CRC patients with strong TGM2 expression.

Note: 2023 Oct;30(10):1346-1354

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Frankfurt (FM01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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