PI-3 kinase-PTEN pathway regulates the expression of E- and N-cadherin in melanoma progression
Bibliographic record
Abstract
3017 Malignant melanoma is the most deadly form of skin cancer, the incidence of which is dramatically increasing in Western countries. Early metastasis is characteristic of melanoma and is associated with poor prognosis as current therapeutic interventions have little influence on survival. Some of the most pertinent molecules involved in the invasion and metastasis of tumors are the cell adhesion molecules (cadherins, catenins, integrins). The expression and interplay among these group of molecules control not only the attachment to ECM and motility on ECM of cells but also regulate numerous signal transduction pathways involved in regulation of cellular functions. While the expression of E-cadherin is inversely associated with melanoma progression to an aggressive phenotype, the expression of N-cadherin is in direct association with this progression. This profile is also observed in epithelial cancers and the loss of expression of E-cadherin is often seen to occur when there is a loss in expression or activity of PTEN resulting in a constitutive activation of PI-3 kinase pathway. In this study we compare the expression of key adhesion molecules in two melanoma cell lines (A375, A2058) to that of primary melanocytes (HEMa-LP). Our results indicate that while there is substantial expression of E-cadherin in melanocytes, there is little to no expression of the protein in the melanoma cell lines. On the other hand, there is a significant expression of N-cadherin in the melanoma lines, especially in the metastatic A2058, with no expression in melanocytes. β-catenin expression is higher in melanoma cell lines with the highest expression being observed in the A2058 line. The A2058 cell line is a PTEN-null cell line exhibiting a constitutively high expression of phospho-Akt. Re-expression of PTEN-wt into A2058 results in the appearance of E-cadherin expression and an associated disappearance in the expression of N-cadherin. The cellular morphology of the A2058 cells also changes from a fibroblastic/spindle shaped appearance to an epithelial/melanocyte type appearance. Although an alteration in the total cellular expression levels of β-catenin is not observed with introduction of PTEN-wt, immunofluorescence studies showed an alteration in the localization of β-catenin from a primarily nuclear localization in the PTEN-null A2058 cells to a mostly peripheral cell surface localization in the PTEN-expressing A2058 cells. Decreased cellular and nuclear levels of phospho-Akt-Ser-473 in the PTEN expressing A2058 cells, in the absence of any alteration in Akt protein expression, indicates a controlled regulation of a previously constitutely active PI-3 kinase pathway. Our results suggest that PI-3 kinase pathway is involved in regulating the adhesion molecule phenotype in melanoma and hence is involved in regulating progression to invasive phenotype of this tumor.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".