XIAP induces inflammation and promotes colorectal cancer progression.
11 affiliations
- 1University of Cologne, Faculty of Medicine and University Hospital of Cologne, Department of General, Visceral, Thoracic and Transplantation Surgery, Cologne, Germany. [email protected].
- 2University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute for Molecular Immunology, Cologne, Germany.
- 3Max Planck Institute for Metabolism Research, Department of Obesity and Cancer, Cologne, Germany.
- 4University of Cologne, Faculty of Medicine and University Hospital of Cologne, Department of General, Visceral, Thoracic and Transplantation Surgery, Cologne, Germany.
- 5University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, Cologne, Germany.
- 6University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
- 7University Hospital Heidelberg, University Heidelberg, Department of General, Visceral and Transplantation Surgery, Heidelberg, Germany.
- 8University of Cologne, Faculty of Medicine and University Hospital of Cologne, Department of Neurosurgery, Cologne, Germany.
- 9University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany.
- 10Immunology and Early Discovery Biochemistry, Genentech, South San Francisco, CA, USA.
- 11University of Cologne, Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), Cologne, Germany.
Abstract
Colorectal cancer (CRC) is one of the most diagnosed malignancies worldwide, with chronic inflammation playing a critical role in its pathogenesis and progression. Surgery represents the primary treatment option, though some patients suffer from relapse, leading to considerable morbidity and mortality. A better molecular understanding of CRC pathogenesis is therefore essential for identifying patients at increased risk of recurrence and improving clinical management. Here we identified the X-linked inhibitor of apoptosis protein (XIAP) as an independent predictor of overall survival in primary resected CRC patients. To model CRC patients with low versus high XIAP expression, we established conditional mouse lines for intestinal epithelial cell (IECs)-specific Xiap knock-out and XIAP knock-in, and employed a colitis-associated murine model for CRC. We found that XIAP promotes inflammatory signalling and exacerbates colitis-driven colorectal tumorigenesis by shaping a distinct tumor inflammatory microenvironment characterized by increased immune-cell infiltration, including neutrophils, and enhanced vascularisation. The pro-inflammatory role of XIAP was further validated in CRC patient-derived organoids and human CRC tumor specimens. Collectively, our findings identify XIAP as a potential biomarker of CRC-associated inflammation and a candidate marker for identifying patients at increased risk of disease recurrence. Moreover, these results provide a rationale for exploring XIAP-targeting strategies as a potential component of multimodal therapeutic approaches for CRC.
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BibTeX
@article{schiffmann2026xiap,
title = {{XIAP induces inflammation and promotes colorectal cancer progression.}},
author = {Lars M Schiffmann and Mila Daoud and Claudia Maria Wunderlich and Fabian Schorn and Johanna Stachelscheid and Pia Nora Broxtermann and Marie-Christine Albert and M Siebenbürger and Heike Göbel and Ulrike Göbel and Ali T Abdallah and J Paul Werthenbach and Jens Michael Seeger and Naita M Wirsik and Karl Knipper and Su Ir Lyu and Thomas Schmidt and Nikolai Schleußner and Uraz Yasar and Christian Goddemeier and Stephanie T Jünger and Hans A Schlößer and Georg Dieplinger and Thomas Zander and Hakan Alakus and Hans F Fuchs and Florian Gebauer and Christiane J Bruns and Domagoj Vucic and Alexander Quaas and Melanie Fritsch and Frank Thomas Wunderlich and Hamid Kashkar},
journal = {Cell death \& disease},
year = {2026},
month = nov,
doi = {10.1038/s41419-026-09391-9},
url = {https://europepmc.org/article/MED/42971958},
note = {CC BY},
}
RIS
TY - JOUR
TI - XIAP induces inflammation and promotes colorectal cancer progression.
AU - Lars M Schiffmann
AU - Mila Daoud
AU - Claudia Maria Wunderlich
AU - Fabian Schorn
AU - Johanna Stachelscheid
AU - Pia Nora Broxtermann
AU - Marie-Christine Albert
AU - M Siebenbürger
AU - Heike Göbel
AU - Ulrike Göbel
AU - Ali T Abdallah
AU - J Paul Werthenbach
AU - Jens Michael Seeger
AU - Naita M Wirsik
AU - Karl Knipper
AU - Su Ir Lyu
AU - Thomas Schmidt
AU - Nikolai Schleußner
AU - Uraz Yasar
AU - Christian Goddemeier
AU - Stephanie T Jünger
AU - Hans A Schlößer
AU - Georg Dieplinger
AU - Thomas Zander
AU - Hakan Alakus
AU - Hans F Fuchs
AU - Florian Gebauer
AU - Christiane J Bruns
AU - Domagoj Vucic
AU - Alexander Quaas
AU - Melanie Fritsch
AU - Frank Thomas Wunderlich
AU - Hamid Kashkar
PY - 2026
DA - 2026/11/02
JO - Cell death & disease
DO - 10.1038/s41419-026-09391-9
UR - https://europepmc.org/article/MED/42971958
AB - Colorectal cancer (CRC) is one of the most diagnosed malignancies worldwide, with chronic inflammation playing a critical role in its pathogenesis and progression. Surgery represents the primary treatment option, though some patients suffer from relapse, leading to considerable morbidity and mortality. A better molecular understanding of CRC pathogenesis is therefore essential for identifying patients at increased risk of recurrence and improving clinical management. Here we identified the X-linked inhibitor of apoptosis protein (XIAP) as an independent predictor of overall survival in primary resected CRC patients. To model CRC patients with low versus high XIAP expression, we established conditional mouse lines for intestinal epithelial cell (IECs)-specific Xiap knock-out and XIAP knock-in, and employed a colitis-associated murine model for CRC. We found that XIAP promotes inflammatory signalling and exacerbates colitis-driven colorectal tumorigenesis by shaping a distinct tumor inflammatory microenvironment characterized by increased immune-cell infiltration, including neutrophils, and enhanced vascularisation. The pro-inflammatory role of XIAP was further validated in CRC patient-derived organoids and human CRC tumor specimens. Collectively, our findings identify XIAP as a potential biomarker of CRC-associated inflammation and a candidate marker for identifying patients at increased risk of disease recurrence. Moreover, these results provide a rationale for exploring XIAP-targeting strategies as a potential component of multimodal therapeutic approaches for CRC.
SN - 2041-4889
ER -