A role for kinesin-1 subunits KIF5B/KLC1 in regulating epithelial mesenchymal plasticity in breast tumorigenesis
Bibliographic record
Abstract
BACKGROUND: Epithelial mesenchymal plasticity (EMP) is deemed vital in breast cancer progression, metastasis, stemness and resistance to therapy. Therefore, characterizing molecular mechanisms contributing to EMP are in need enabling the development of more advanced therapeutics against breast cancer. While kinesin superfamily proteins (KIFs) are well known for their role in intracellular cargo movement, our knowledge of their function in breast tumorigenesis is still limited. METHODS: Various breast cancer cell lines representing different molecular subtypes were used to determine the role of kinesine-1 subunits KIF5B/KLC1 in regulation of EMP. FINDINGS: In breast cancer, we show that kinesin family member 5B (KIF5B) and its partner protein kinesin light chain 1 (KLC1), subunits of kinesin-1, to play differential roles in regulating EMP and tumorigenesis. Indeed, we found KIF5B to be expressed in triple negative (TN)-basal-like/claudin low breast cancer subtype and to be an inducer of epithelial-mesenchymal transition (EMT), stemness, invasiveness, tumor formation and metastatic colonization. Whereas, we found KLC1 to be expressed in epithelial/luminal breast cancer subtypes and to be a suppressor of EMT, invasion, metastasis and stem cell markers expression as well as to be an inducer of epithelial/luminal phenotype. Interestingly, in TN-basal-like/claudin low cells we found a novel nuclear accumulation of KIF5B and its interaction with the EMT transcriptional regulator Snail1 independent of KLC1. In addition, TGF-β mediated pro-invasive activity was found to be dependent on KIF5B expression. In contrast, the epithelial differentiation factor and EMT suppressor prolactin (PRL) was found to repress KIF5B gene expression and KIF5B-Snail1 nuclear accumulation, but enhanced KLC1 gene expression and KIF5B-KLC1 interaction. INTERPRETATION: Together, these results highlight a new paradigm for kinesin-1 function in breast tumorigenesis by regulating EMP programing and aggressiveness. FUND: This work was supported by the Canadian Institutes of Health Research (operating grants #233437 and 233438) granted to Suhad Ali.
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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) | 0.000 | 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".