Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases
Bibliographic record
Abstract
// Fatma Sfaxi 1,2 , Nathalie Scamuffa 1,2 , Claude Lalou 1,2 , Jia Ma 1,2 , Peter Metrakos 3 , Géraldine Siegfried 1,2 , Hermann Ragg 4 , Andreas Bikfalvi 1,2 , Fabien Calvo 5 , Abdel-Majid Khatib 1,2 1 Université Bordeaux 1, LAMC, Talence, France. 2 INSERM, UMR 1029, F-33405 Talence, France. 3 Department of Surgery, McGill University, Royal Victoria Hospital, McGill University Health Centre, Montreal, H3A 1A1, QC, Canada. 4 Department of Biotechnology, Faculty of Technology, University of Bielefeld, 33501 Bielefeld, Germany. 5 Institut de Génétique Moléculaire, INSERM UMRS 940, Université Paris7, Paris, France. Correspondence: Abdel-Majid Khatib, email: // Keywords : Spn4A, Furin, PC5, PACE4, PC7, mitogenic activity Received : March 14, 2014 Accepted : May 12, 2014 Published : May 13, 2014 Abstract Liver is the most common site of metastasis from colorectal cancers, and liver of patients with liver colorectal metastasis have abnormal levels of the proprotein convertases (PCs). These proteases are involved in the activation and/or expression of various colon cancer-related mediators, making them promising targets in colorectal liver metastasis therapy. Here, we revealed that the serpin Spn4 from Drosophila melanogaster inhibits the activity of all the PCs found in the constitutive secretory pathway and represses the metastatic potential of the colon cancer cells HT-29 and CT-26. In these cells, Spn4A inhibited the processing of the PCs substrates IGF-1R and PDGF-A that associated their reduced anchorage-independent growth, invasiveness and survival in response to apoptotic agents. In vivo, Spn4A-expressing tumor cells showed repressed subcutaneous tumor development and liver metastases formation in response to their intrasplenic inoculation. In these cells Spn4A induced the expression of molecules with anti-metastatic functions and inhibited expression of pro-tumorigenic molecules. Taken together, our findings identify Spn4A as the only endogenous inhibitor of all the constitutive secretory pathway PCs, which is able to repress the metastatic potential of colon cancer cells. These results suggest the potential use of Spn4A and/or derivates as a useful adduct colorectal liver metastasis prevention.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".