Abstract 2249: N- and C-terminal peptides of the tumor suppressor protein IGFBP7 differentially induce growth arrest or senescence in breast cancer cells
Bibliographic record
Abstract
Abstract N- and C-terminal peptides of the tumor suppressor protein IGFBP7 differentially induce growth arrest or senescence in breast cancer cells Tania Benatar, Yutaka Amemiya, Valentina Evdokimova, Wenyi Yang and Arun Seth We have previously shown that insulin-like growth factor binding protein 7 (IGFBP7) is a tumor suppressor in breast cancer. IGFBP7 treatment resulted in breast cancer cell growth inhibition via induction of senescence and apoptotic pathways. Xenografted tumors overexpressing IGFBP7 were significantly growth-impaired as were the xenografted tumors treated systemically with purified IGFBP7. Given its low toxicity and high selectivity towards cancerous tissues, IGFBP7 is considered to be a promising anticancer agent. Its anticancer efficacy was further strengthened by our recent findings showing that the N-terminal 97 amino acid IGFBP7 domain is required for blocking Insulin-like Growth Factor 1 Receptor (IGF1R) activity and downstream PI3K-AKT-mTOR signaling. To further identify parameters that could predict IGFBP7-responsiveness in breast tumors, a variety of breast cancer cell lines were examined for growth responses and signaling pathways in response to IGFBP7 treatment. In this study, we found that treatment of some aggressive breast cancer cell lines, with IGFBP7 resulted in its proteolytic cleavage between Lys-97 and Ala-98 thus creating N-terminal and C-terminal specific peptides. While both the N- and C-terminal peptides were capable of growth inhibition, only the C-terminal fragment was efficient at inducing cellular senescence. The IGFBP7-responsiveness of breast cancer cell lines was a direct consequence of their ability to process IGFBP7. In order to compare which genes and pathways arewere affected by IGFBP7-full length (FL) versus cleaved form (CF) overexpression, we performed transcriptome Next- Generation sequencing from parental MDA-MB-468, MDA-MB-468 overexpressing full length (FL) of IGFBP7-FL or overexpressing cleaved form (CF) of IGFBP7-CF. We obtained 2486 gene differences for FL expressers and 3953 differences for CF expressers using mapped reads with a quality of 10 and at least a two-fold change. Of the thirteen breast cancer-associated genes that were differentially expressed between MDA-MB-468 cells and FL or CF expressing cells, most (10/13) were further enhanced upon IGFBP7-CF overexpression. Taken together, Tthese results indicate that IGFBP7s distinct N- and C-terminal functional domains, are ideal candidates for the development of companion theranostiitcs, as the ability of the tumor to effectively cleave IGFBP7 will determine efficacy of treatment. Citation Format: Tania C. Benatar, Yutaka Amemiya, Valentina Evdokimova, Wenyi Yang, Arun Seth. N- and C-terminal peptides of the tumor suppressor protein IGFBP7 differentially induce growth arrest or senescence in breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2249. doi:10.1158/1538-7445.AM2014-2249
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 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) | 0.002 | 0.001 |
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".