ShcD adaptor protein drives invasion of triple negative breast cancer cells by aberrant activation of EGFR signaling
Bibliographic record
Abstract
Triple-negative breast cancer (TNBC) is highly metastatic and presents clinical challenges given the lack of targeted therapies. Here, we report that the ShcD phosphotyrosine adaptor protein is upregulated in TNBC, and its expression correlates with overall reduced patient survival and decreased response to chemotherapy. In human breast cancer cells, we demonstrate that ShcD expression promotes cell invasion and reduces adhesion, and that these effects are abrogated by mutating the ShcD phosphotyrosine binding (PTB) domain. Similarly, in a three-dimensional assembloid model, ShcD-expressing spheroids derived from brain metastatic TNBC cells show enhanced infiltration into cerebral organoids. Using a proteomic screen for ShcD binding partners, we identify multiple components of epidermal growth factor receptor (EGFR) signaling and confirm these interactions with ShcD but not the PTB mutant. Interestingly, the ShcD interactome correlates with EGFR tyrosine kinase inhibitor resistance, in line with our findings that ShcD overexpression results in hyperphosphorylation of EGFR while ShcD knockout or PTB mutation reverts this response. Lastly, pharmacological inhibition of the ShcD PTB domain using indomethacin in TNBC cells decreases EGFR binding and hyperphosphorylation and reduces cell invasion. Altogether, our results identify ShcD as a potential contributor to metastasis in TNBC, and they provide a molecular basis for clinical targeting of adaptor proteins.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".