FOXC1 is Over‐expressed and is More Stable in Triple Negative/Basal‐Like Breast Cancer
Bibliographic record
Abstract
Rapidly accumulating evidence implicates forkhead box C1 ( FOXC1 ) in Triple Negative Breast Cancer (TNBC), particularly in Basal‐Like Breast cancer (BLBC). Recently additional studies have demonstrating that FOXC1 is also a major player in hepatocellular carcinoma (HCC), endometrial cancer, Hodgkin's lymphoma (HL), non‐Hodgkin's lymphoma (NHL), and others. The FOXC1 gene encodes a transcription factor that is crucial to mesodermal, neural crest, and ocular development. Loss of function mutations in FOXC1 have been shown to cause autosomal dominantly inherited Axenfeld‐Rieger's Syndrome (ARS), a developmental disorder associated in eye anomalies and glaucoma. Interestingly, while FOXC1 missense mutations that cause ARS reduce FOXC1 activity, increased FOXC1 function now appears to be often linked to more aggressive cancer phenotypes in TN/BL‐BC, HCC, HL, and NHL. We have investigated the mechanism(s) by which FOXC1 activity is increased in BLBC. Samples were obtained from TNBC tumors, Triple Positive Breast Cancer (TPBC) tumors or from breast tissue from normal patients. Using quantitative PCR, we found that FOXC1 was significantly over‐expressed in TNBC patients as compared to controls. In contrast, FOXC1 mRNA was significantly less expressed in TPBC samples as compared to either control or TNBC samples. FOXC1 protein half‐life was significantly longer in the TNBC/BLBC cell lines (HS 587T and BT 549) compared to FOXC1 protein's half‐life in HeLa cells. Studies of FOXC1 Copy‐number variation (CNV) in TNBC/BLBC cell lines reveals that cell lines that have higher levels of FOXC1 protein (HS 587T, BT‐549) have extra copies of FOXC1 . This contrasts with a cell line with lower expression of FOXC1 protein, MDA‐MB‐231, which may be explained by a deletion of FOXC1 in this TNBC cell line. Our results suggest that increased FOXC1 function in TNBC/BLBC results from over‐expression of FOXC1 in tumors of TNBC patients that appears to be the result of changes to FOXC1 stability and amplification of FOXC1 copy number. We predict that understanding the mechanism(s) underlying FOXC1's activation in cancer could aid in designing improved therapies for TNBC patients. Support or Funding Information Verag Donation to MAW This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.001 | 0.001 |
| 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) | 0.002 | 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 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".