Cx26 inhibits breast MDA-MB-435 cell tumorigenic properties by a gap junctional intercellular communication-independent mechanism
Bibliographic record
Abstract
It has been well established that the restoration of connexin expression in tumor cells often leads to a partial reversion of tumor cell phenotypes and increased growth control. In this study, a less-aggressive variant of MDA-MB-435 cells obtained from the MDA-MB-435 cell line was engineered to express gap junctional intercellular communication (GJIC)-competent Cx26, a GJIC-incompetent cell surface transported GFP-Cx26 chimera, or a Golgi apparatus-localized, disease-linked Cx26 mutant (D66H). Collectively, these cell lines were designed to establish whether Cx26 regulates tumor properties, such as migration, invasion and growth, by (i) a GJIC-dependent pathway; (ii) a mechanism requiring Cx26 transport to the cell surface; or (iii) a mechanism where Cx26 expression alone was sufficient. The expression of Cx26 and green fluorescent protein (GFP)-Cx26 decreased cell proliferation while all three Cx26 variants inhibited anchorage-independent cell growth. All three Cx26 variants also altered the distribution of filamentous actin and significantly reduced cell migration, while only the D66H mutant failed to inhibit cell invasion through matrigel. Furthermore, expression of all the Cx26 variants reduced the levels of total beta1 integrin, and decreased the activity of matrix metalloproteinase-9 (MMP-9) while increasing tissue inhibitors of MMP-1 (TIMP-1) activity. Interestingly, the expression of Cx43 regulated the same gene products without significantly affecting the tumorigenic properties of the MDA-MB-435 cells. Together, these results suggest that Cx26 expression, independent of the necessity for gap junctional intercellular communication, partially reverted MDA-MB-435 cell properties associated with tumorigenesis, and regulated the expression of genes important in cell migration and invasion.
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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".