Abstract 2656: Sec23b governs the migration of MDA-MB-231 breast cancer cells by regulating collagen I processing and secretion
Bibliographic record
Abstract
Abstract Cancer metastasis is a complex, multi-step process that begins with the dissociation of primary cancer cells from their original site. These cells then migrate to distant areas, where they establish colonies and undergo uncontrolled proliferation at secondary locations. Thus, dysregulation of cell migration is one of the hallmarks of solid tumour metastasis. Given that the actin cytoskeleton plays crucial roles in normal cell migration, we developed a robust method that combines an amino acid sequence that binds to actin (LifeAct) with biotin-mediated proximal labelling (BioID) to identify actin-binding proteins. Specifically, to identify actin-associated protein complexes during the early stages of cells migrating into scratched areas, we conjugated LifeAct with the newest derivation of BioID (miniTurbo-LifeAct-BioID) and controlled its expression with doxycycline in MDA-MB-231 cells. After inducing cell migration by scratch wounding, we allowed cells to migrate into the scratched areas for 1.5 hours then pulse-labelled with biotin for 30 minutes. As controls, using the same system, we labelled actin-associated proteins in resting cells and in cells that had been treated with cytochalasin D (CD) to depolymerize actin filaments. Compared to the untreated cells, the CD-treated cells increased labelling of the G-actin binding proteins (e.g., profilin and JMY) while decreased labelling of the F-actin binding proteins (e.g., Coronin2A and ABLIM1/ABLIM2/ ABLIM3), validating the ability of miniTurbo-LifeAct-BioID to detect dynamic changes in cytoskeleton-associated protein complexes. By comparing miniTurbo-LifeAct-BioID labelled proteins in migrating versus stationary cells, eighteen proteins were significantly more biotin labelled and eight proteins were less biotin labelled. Unexpectedly, Sec23b, a component of the COPII secretion complex, was labelled to a greater extent in cells migrating into scratched areas. Depletion of Sec23b increased secretion of procollagen I but decreased deposition of collagen I filaments. Interestingly, the reduced migration of cells depleted of Sec23b was rescued by collagen I but not by fibronectin or gelatin. Based on our findings, metastatic breast cancer MDA-MB-231 cells appear to control the secretion and processing of collagen I to govern their extracellular matrix organization for efficient cell migration. Citation Format: E. Emily Joo, Audrey Astori, Jonathan St-Germain, Brian Raught, Michael F. Olson. Sec23b governs the migration of MDA-MB-231 breast cancer cells by regulating collagen I processing and secretion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2656.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".