Transglutaminase 2 is associated with adverse colorectal cancer survival and represents a therapeutic target.

Autor: Malkomes P; Department for General, Visceral, Transplant and Thoracic Surgery, Goethe University, Frankfurt am Main, Germany.; Frankfurt Cancer Institute, Frankfurt am Main, Germany.; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany., Lunger I; Department for General, Visceral, Transplant and Thoracic Surgery, Goethe University, Frankfurt am Main, Germany.; Department of Medicine II, Hematology/Oncology, Goethe University, Frankfurt am Main, Germany., Oppermann E; Department for General, Visceral, Transplant and Thoracic Surgery, Goethe University, Frankfurt am Main, Germany., Lorenz J; Department for General, Visceral, Transplant and Thoracic Surgery, Goethe University, Frankfurt am Main, Germany., Faqar-Uz-Zaman SF; Department for General, Visceral, Transplant and Thoracic Surgery, Goethe University, Frankfurt am Main, Germany., Han J; Department for General, Visceral, Transplant and Thoracic Surgery, Goethe University, Frankfurt am Main, Germany., Bothur S; Department of Medicine II, Hematology/Oncology, Goethe University, Frankfurt am Main, Germany., Ziegler P; Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.; University Cancer Center (UCT), Frankfurt am Main, Germany., Bankov K; Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.; University Cancer Center (UCT), Frankfurt am Main, Germany., Wild P; Dr. Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.; University Cancer Center (UCT), Frankfurt am Main, Germany., Bechstein WO; Department for General, Visceral, Transplant and Thoracic Surgery, Goethe University, Frankfurt am Main, Germany., Rieger MA; Frankfurt Cancer Institute, Frankfurt am Main, Germany. m.rieger@em.uni-frankfurt.de.; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. m.rieger@em.uni-frankfurt.de.; Department of Medicine II, Hematology/Oncology, Goethe University, Frankfurt am Main, Germany. m.rieger@em.uni-frankfurt.de.; Cardio-Pulmonary-Institute, Frankfurt am Main, Germany. m.rieger@em.uni-frankfurt.de.
Jazyk: angličtina
Zdroj: Cancer gene therapy [Cancer Gene Ther] 2023 Oct; Vol. 30 (10), pp. 1346-1354. Date of Electronic Publication: 2023 Jul 13.
DOI: 10.1038/s41417-023-00641-y
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: