Research Papers:

Loss of DRO1/CCDC80 in the tumor microenvironment promotes carcinogenesis

Jessica I. Christian _, Agnieszka Pastula, Andreas Herbst, Jens Neumann, Maximilian K. Marschall, Andrea Ofner, Heike Zierahn, Marlon R. Schneider, Eckhard Wolf, Michael Quante and Frank T. Kolligs

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Oncotarget. 2022; 13:615-627. https://doi.org/10.18632/oncotarget.28084

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Jessica I. Christian1,*, Agnieszka Pastula2,*, Andreas Herbst3,4, Jens Neumann5, Maximilian K. Marschall1, Andrea Ofner3, Heike Zierahn1, Marlon R. Schneider1, Eckhard Wolf1, Michael Quante2 and Frank T. Kolligs3,6,7,8

1 Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig Maximilian University of Munich, Munich 81377, Germany

2 Gastroenterologie II, Klinikum rechts der Isar, Technical University of Munich, Munich 81675, Germany

3 Department of Medicine II, Ludwig Maximilian University of Munich, Munich 81377, Germany

4 Institute of Laboratory Medicine, University Hospital, Ludwig Maximilian University of Munich, Munich 81377, Germany

5 Institute of Pathology, Ludwig Maximilian University of Munich, Munich 80337, Germany

6 German Cancer Consortium (DKTK), Heidelberg 69120, Germany

7 German Cancer Research Center (DKFZ), Heidelberg 69120, Germany

8 Department of Internal Medicine and Gastroenterology, HELIOS Klinikum Berlin-Buch, Berlin 13125, Germany

* These authors contributed equally to this work

Correspondence to:

Jessica I. Christian, email: [email protected]

Keywords: DRO1; CCDC80; colorectal cancer; tumor microenvironment; tumor suppressor

Received: July 09, 2021     Accepted: September 04, 2021     Published: April 11, 2022

Copyright: © 2022 Christian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Tumors are composed of the tumor cells and the surrounding microenvironment. Both are closely interwoven and interact by a complex and multifaceted cross-talk which plays an integral part in tumor initiation, growth, and progression. Dro1/Ccdc80 has been shown to be a potent suppressor of colorectal cancer and ubiquitous inactivation of Dro1/Ccdc80 strongly promoted colorectal carcinogenesis in ApcMin/+ mice and in a chemically-induced colorectal cancer model.

The aim of the present study was to investigate whether Dro1/Ccdc80’s tumor suppressive function is tumor-cell-autonomous. Expression of Dro1/Ccdc80 in cancer cells had no effect on both colon tumor development in ApcMin/+ mice and formation of xenograft tumors. In contrast, DRO1/CCDC80 loss in the microenvironment strongly increased tumor growth in xenograft models, inhibited cancer cell apoptosis, and promoted intestinal epithelial cell migration. Moreover, stromal Dro1/Ccdc80 inactivation facilitated formation of intestinal epithelial organoids. Expression analyses showed Dro1/Ccdc80 to be significantly down-regulated in murine gastric cancer associated fibroblasts, in ApcMin/+ colon tumor primary stromal cells and in microdissected stroma from human colorectal cancer compared to normal, non-tumor stroma. Our results demonstrate epithelial derived DRO1/CCDC80 to be dispensable for intestinal tissue homeostasis and identify Dro1/Ccdc80 as tumor suppressor in the tumor microenvironment.

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