Prodomain of the proprotein convertase subtilisin/kexin Furin (ppFurin) protects from tumor progression and metastasis
Bibliographic record
Abstract
Proteolytic maturation of various precursor proteins by the proprotein convertase Furin is now considered as a crucial step in tumor progression and metastasis. Here, we report the repression of the malignant and metastatic potential of carcinoma cells by the prodomain region of Furin (ppFurin), a naturally occurring inhibitor of this convertase. Overexpression of ppFurin in carcinoma cells in a stable manner significantly reduced their convertase activity and ability to mediate processing of the Furin cancer-related substrates platelet-derived growth factor (PDGF)-A and insulin-like growth factor-I receptor precursors. Unprocessed platelet-derived growth factor-A produced by ppFurin expressing cells failed to induce the activation of Akt in the platelet-derived growth factor receptor-expressing cells NIH BALB/c-3T3 and treatment of ppFurin expressing cells with insulin-like growth factor-I failed to induce Akt phosphorylation, compared with controls. The malignant potential of ppFurin expressing cells was significantly reduced as revealed by the loss of anchorage-independent growth and survival that associated their increased chemosensitivity. In vivo, comparative studies revealed that expression of ppFurin in the carcinoma cells MDA-MB-231 and CT-26 cells inhibited tumor growth when subcutaneously inoculated in nude mice. The use of an experimental liver colorectal metastasis model revealed the reduced ability of metastatic carcinoma CT-26 cells to colonize the liver in response to intrasplenic/portal inoculation. Further analyses revealed reduced Furin activity in tumors derived from intrasplenic inoculated mice with ppFurin expressing CT-26 cells. This finding highlights the role of Furin in the malignant and metastatic potential of tumor cells and suggests the possible consideration of using its naturally occurring inhibitor ppFurin in anticancer therapy.
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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".