CD44 modulates cofilin expression in human colon cancer cells
Bibliographic record
Abstract
3442 Colon cancer is among the leading causes of cancer death in North America. Dysregulation of the colonic crypt homeostasis is evident in the early stage of cancer. Moreover, cytoskeletal rearrangement of actin also plays a crucial role in morphological changes during neoplastic transformation events, including impairment of apoptosis. CD44, an adhesion and antiapoptotic molecule is overexpressed in colon cancer and is known to interact with certain cytoskeletal proteins. Cofilin is an actin binding protein and is involved with the directional motility of cells. In the present study, we asked whether the upregulation of CD44, has an effect of cofilin and proteins acting downstream from them. We used a human colon cancer cell line, HT29, which expresses both the standard and variant isoforms of CD44, HT29 where CD44 expression was inhibited by siRNA, and the colon from CD44 knockout and control mice. Western blot analysis of lysates from HT29 cells where CD44 levels were downregulated by siRNA, showed increased level of cofilin expression compared to vector control. The same set of lysates also had increased level of AKT phosphorylation. Immunocytochemistry showed that cofilin expression in colonic epithelial cells was greater in HT29 cells where CD44 was inhibited by siRNA, as compared to vector controls. Experiments using LY294002, an inhibitor of AKT phosphorylation, indicated that cofilin is stabilized by phosphorylated AKT. Knockout mice colon and colonic crypts isolated from them exhibit greater levels of active caspase 3, as compared to wild type mice. Western blot analysis of CD44 knock out mice colon lysates exhibited slightly lower levels of cofilin as compared to the colon lysates from wild type mice. This is in spite of having higher levels of AKT phosphorylation suggesting that other compensatory pathways operate in vivo. Cofilin expression is thus mechanistically associated with CD44 expression. AKT-phosphorylation and caspase 3 activation may have a key role in cofilin modulation. Given the well defined roles of CD44, phosphorylated AKT and caspase 3 in apoptosis and cancer, their role in modulating cofilin expression can cause alterations in the directional motility of tumor cells.
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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) | 0.002 | 0.001 |
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".