Epithelial Src homology region 2 domain–containing phosphatase‐1 restrains intestinal growth, secretory cell differentiation, and tumorigenesis
Bibliographic record
Abstract
ABSTRACT Shp‐1 (Src homology region 2 domain‐containing protein tyrosine phosphatase‐1) is a phosphatase that is highly expressed in hematopoietic and epithelial cells. Whereas its function is largely characterized in hematopoietic cells, its role in epithelial cells, such as intestinal epithelial cells (IECs), is not well known. Here, we generated mice with an IEC‐specific knockout of Shp‐1 (Src homology region 2 domain–containing phosphatase‐1; Shp‐1 IEC‐KO ). We showed that the loss of epithelial Shp‐1 leads to an intestinalomegaly that is associated with an increase in epithelial cell proliferation and size. Histologic analysis demonstrates significant perturbation of the crypt‐villus architecture with an apparent increase in the number of goblet and Paneth cells and increased expression of their respective markers {Muc2 (mucin 2), aDef, and Sox9 [SRY (sex determining region Y)‐box 9]}. Expansion of intermediate cells—common progenitors of goblet and Paneth cell lineages—is also observed in Shp‐1 IEC‐KO mice. Although sustained activation of Wnt/β‐catenin and PI3K/Akt/mammalian target of rapamycin signaling is observed, Shp‐1 IEC‐KO mice fail to develop any intestinal tumors after 15 mo; however, the loss of Shp‐1 in IECs markedly enhances tumor load Apc Min/+ mice. These findings show a novel role for Shp‐1 in the regulation of IEC growth and secretory lineage allocation, possibly via modulation of PI3K/Akt‐dependent signaling pathways. Finally, Shp‐1 does not function as a classic tumor suppressor gene in the intestinal epithelium.—Leblanc, C., Langlois, M.‐J., Coulombe, G., Vaillancourt‐Lavigueur, V., Jones, C., Carrier, J. C., Boudreau, F., Rivard, N. Epithelial Src homology region 2 domain–containing phosphatase‐1 restrains intestinal growth, secretory cell differentiation, and tumorigenesis. FASEB J . 31, 3512–3526 (2017). www.fasebj.org
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".