Multiple post-translational modifications of E-cadherin during ER stress and apoptosis
Bibliographic record
Abstract
188 As a vital cell adhesion molecule, E-cadherin plays an important role in the suppression of tumorigenesis, tumor invasion and metastasis. Because stress and apoptosis are common events in tumors, we examined the regulation of E-cadherin expression during endoplasmic reticulum (ER) stress and apoptosis in the MCF-7 human breast cancer cell line. We used different agents to elicit ER stress and analyzed alterations of E-cadherin in MCF-7 cells by western blotting. To assay glycosylation, wheat germ agglutinin (WGA)-agarose was used to precipitate glycoproteins from cell lysates. To differentiate O-linked and N-linked glycosylation, N-linked carbohydrate was removed from samples by digestion with PNGase. Digestion with the proprotein convertase furin was used to examine pro-protein processing. Here we report that after the induction of ER stress by either thapsigargin or brefeldin A, as well as after induction of apoptosis by a cell-permeable ceramide derivative, both the mature form of E-cadherin (120 kDa) and a multiply modified form of E-cadherin (135 kDa) were detected in MCF-7 cells. PNGase digestion revealed that both forms are N-glycosylated. However, the 135 kDa form bound WGA even after PNGase digestion. Furthermore, pretreatment with tunicamycin to inhibit N-glycosylation did not reduce binding of the 135 kDa form to WGA confirming this form is also O-glycosylated. This form of E-cadherin was cleaved in vitro by furin into a mature form (120 KDa) suggesting it contains an unprocessed pro-region. Moreover, inhibition of furin generated a 135 kDa form of E-cadherin in unstressed cells. Therefore, upregulation of O-glycosylation and inhibition of proprotein processing of E-cadherin occur in response to some ER stress and apoptosis pathways. These modifications block E-cadherin cell surface transport suggesting they might lead to increased metastasis.
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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) | 0.001 | 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 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".