7. Dkk‐1/Ror2 and Wnt5a/Ror2 Production of CDX2: Defining Intestinal Adenocarcinoma
Bibliographic record
Abstract
Wnt signaling regulates cell proliferation and differentiation through ahomeostasis of canonical and noncanonical pathways. Aberrant Wnt signaling induces intestinal adenocarcinoma by promoting stem cell hyperproliferation. In the intestine, Wnt5a binds to its receptor Ror2 to increase the caudal homeobox factor CDX2, a transcriptional activator of intestinal differentiation. Contradictorily, it was also shown that Ror2 alone is overexpressed in adenocarcinoma, and that Ror2 alone will mediate CDX2 increase in vitro. The purpose of this research is to determine how CDX2 is increased by Ror2 alone and Wnt5a/Ror2. Human colon adenocarcinoma cells (HT‐29, SW‐480, and RKO) were used as an in vitro epithelial model. HT‐29 cells constitutively express the signaling protein Dickkopf‐1, whereas SW‐480 and RKO do not. Wnt5a/rhDkk‐1 was used to treat Ror2 or siRor2 transfected cells primed with MAP kinase pharmacological inhibitors. The results show that CDX2 was increased after Ror2 overexpression in HT29, but not RKO/SW480 cells. Further addition of Dkk‐1 to RKO/SW480 cells resulted in CDX2 increase. Pharmacological inhibition of p38 MAPK, casein kinase 1, or Src kinase decreased CDX2 protein ~24% in Dkk‐1/Ror2 cells, while inhibition of JNK, casein kinase 1, or Src kinase in Wnt5a/Ror2 cells decreased CDX2 protein ~35%. The conclusion is that Ror2 increase in CDX2 protein is dependent on Dkk‐1 or Wnt5a. Dkk‐1/Ror2 CDX2 production is mediated by the MAP kinases p38, CK1, and Src. Wnt5a/Ror2 increases in CDX2 require JNK activation, but not p38 MAPK. Different signaling pathways, dependent on the presence of Dkk1/Wnt5a, offer an explanation for the seemingly contradictory increase in Ror2 alone seen in intestinal adenocarcinoma.
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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 | 0.002 | 0.001 |
| 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 | 0.001 |
| 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".