| Title |
Inactivation of JNK2 as carcinogenic factor in colitis-associated and sporadic colorectal carcinogenesis
|
|---|---|
| Published in |
Carcinogenesis, April 2017
|
| DOI | 10.1093/carcin/bgx032 |
| Pubmed ID | |
| Authors |
Wiebke Lessel, Andrew Silver, Doerthe Jechorek, Thomas Guenther, Friedrich-Wilhelm Roehl, Thomas Kalinski, Albert Roessner, Angela Poehlmann-Nitsche |
| Abstract |
We recently reported that dysregulated c-Jun N-terminal kinases (JNK) activity causes defective cell cycle checkpoint control, inducing neoplastic transformation in a cellular ulcerative colitis (UC) model. In the quiescent chronic phase of UC, p-p54 JNK was down-regulated and p-p46 JNK was up-regulated. Both were up-regulated in the acute phase. Consequently, increased p21WAF1 and γ-H2AX, two JNK-regulated proteins, induced cell cycle arrest. Their down-regulation led to checkpoint override, causing increased proliferation and undetected DNA damage in quiescent chronic phase, all characteristics of tumorigenesis. We investigated expression of p-JNK2, p-JNK1-3, p21WAF1, γ-H2AX, and Ki67 by immunohistochemistry in cases of quiescent UC (QUC), active UC (AUC), UC-dysplasia, and UC-related colorectal carcinoma (UC-CRC). Comparison was made to normal healthy colorectal mucosa, sporadic adenoma and colorectal carcinoma (CRC), diverticulitis, and Crohns disease (CD). We found p-JNK2 up-regulation in AUC and its early down-regulation in UC-CRC and CRC carcinogenesis. With down-regulated p-JNK2, p21WAF1 was also decreased. Ki67 was inversely expressed, showing increased proliferation early in UC-CRC and CRC carcinogenesis. p-JNK1-3 was increased in AUC and QUC. Less increased γ H2AX in UC-CRC compared to CRC gave evidence that colitis-triggered inflammation masks DNA damage, thus contributing to neoplastic transformation. We hypothesize that JNK-dependent cell cycle arrest is important in AUC, while chronic inflammation causes dysregulated JNK activity in quiescent phase that may contribute to checkpoint override, promoting UC carcinogenesis. We suggest restoring p-JNK2 expression as a novel therapeutic strategy to early prevent the development of UC-related cancer. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 22 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 5 | 23% |
| Researcher | 3 | 14% |
| Student > Bachelor | 2 | 9% |
| Librarian | 1 | 5% |
| Lecturer | 1 | 5% |
| Other | 2 | 9% |
| Unknown | 8 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 36% |
| Social Sciences | 2 | 9% |
| Agricultural and Biological Sciences | 1 | 5% |
| Biochemistry, Genetics and Molecular Biology | 1 | 5% |
| Computer Science | 1 | 5% |
| Other | 0 | 0% |
| Unknown | 9 | 41% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 April 2017.
All research outputs
#20,413,129
of 22,963,381 outputs
Outputs from Carcinogenesis
#4,454
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Outputs of similar age
#269,833
of 309,563 outputs
Outputs of similar age from Carcinogenesis
#19
of 23 outputs
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