Abstract 2453 The Copper Network of the Cancer Metastasis Modulator MEMO1
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Bibliographic record
Abstract
MEMO1 is an evolutionary conserved protein implicated in many biological processes, however its primary molecular function remains unknown. Importantly, MEMO1 is overexpressed in many types of cancer, in particular, in breast cancer and lung cancer, and modulates cancer metastasis through altered cell motility. MEMO1 has been reported to be a copper-dependent redox-active protein. We have shown that purified MEMO1 binds copper or iron in the coordination mode characteristic of iron-containing dioxygenases. To understand the functional role of MEMO1, we have analyzed its genetic interactions using DepMap gene essentiality data and found multiple iron and copper related genes exhibiting genetic relationships with MEMO1. We have experimentally validated some of the genetic interactions using shRNA gene knockdowns. Interestingly, most of the metal related interactions of MEMO1 are of the gain-of-function type. The copper related genes showing interactions with MEMO1 fall into three main groups by function: (i) cytochrome c oxidase assembly factors (ii) cell adhesion and communication, and (iii) copper storage and transport. Although, in the cell cytosol, MEMO1 is likely to predominantly bind iron, its ability to bind either iron or copper in vitro and its network of iron and copper related genetic interactions suggest an intriguing possibility of a functional switch triggered by copper binding in a specific local environment within the cell. Taken together, our results suggest a key role for MEMO1 in regulating metal homeostasis in the cell. This research was supported by the Canadian Institutes of Health Research Project grant PJT-178246, Natural Sciences and Engineering Council of Canada Discovery grant RGPIN-782 2017-06822 to O.Y.D. and Canadian Institute of Health Research grant PJT-156309 and Canada Foundation for Innovation grant to F.J.V.
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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) | 0.001 | 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 it