Investigating the Role of Porcupine and WNTless: Components of WNT Signalling Pathway in Response to Endoplasmic Reticulum, Oxidative, Hypoxia and Environmental Toxins Stesses
Bibliographic record
Abstract
Porcupine (PORCN) and WNTless (WLS) are factors that control the production of WNT; a protein involved in the early stages of colon cancer development.The WNT proteins play a role in stem cell development and cell differentiation.However, the response of PORCN and WLS to stressors remains to be studied.Previously, we investigated how modifications of PORCN and WLS result in changes in WNT expression and secretion from cells under stress conditions that are found in the tumor microenvironment (hypoxia, oxidative stress, endoplasmic reticulum (ER) stress).The mRNA and protein expression of both PORCN and WLS were notably altered with treatments in human colon cancer (HCT116) cells and human intestinal epithelial (HIEC-6) cells.Our results demonstrated significant changes in expression, which led us to investigate the role of different transcription factors during stresses including (GRP78, HIF1α, NFE2L1, NFEL2L2 and MT1).These transcription factors were altered both at levels of the translation and transcription, when overexpressed by PORCN, WLS and WNT3A.WNT and PORCN levels significantly increased at translation and transcriptional levels when overexpressed by PORCN, WLS and WNT3A.WNT and PORCN undergo palmitoyleation; a modification implicated in cancer cell signalling.The inhibition of palmitoyleation by 2-bromohexdecanoic acid (2-BHDA) resulted in a decrease in the modified forms of PORCN in HCT116 cells.Furthermore, the data showed that palmitoyleation plays an essential role in the expression of WNT proteins; specifically, inhibiting WNT3A and decreasing WLS protein expression in HCT116 cells.However, WLS and WNT3A are modified by N-linked glycosylation.Emerging evidence indicates the critical role of glycosylation in tumor aggressiveness, progression, and metastasis.Cell I would like to extend my thanks to my department.The lab coordinators Mastaneh
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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 | 0.000 |
| 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".