Abstract 1087: Semaphorin 3C drives invasiveness in prostate cells through epithelial-to-mesenchymal transition and stemness
Bibliographic record
Abstract
Abstract Our work sets out to show that semaphorin 3C is a driver of epithelial-to-mesenchymal transition and stemness in prostate cancer. Prostate cancer (PCa) is among the most commonly-occurring non-cutaneous cancers in men. Local non-invasive PCa is highly treatable but limited treatment options exist for those with locally-advanced and metastatic forms of the disease underscoring the need to identify mechanisms mediating PCa progression. The semaphorins are a large grouping of membrane-associated or secreted chemotactic proteins whose normal functions reside in embryogenesis and development where they are responsible for directing cell movement. Semaphorins act through autocrine, paracrine, and juxtacrine signaling and have been implicated in a broad range of biological functions ranging from tissue morphogenesis to immunity; altered semaphorin expression has also been observed in numerous cancers. One member of the class 3 semaphorins, semaphorin 3C (SEMA3C), has been implicated in several forms of cancer and its increased expression is correlated with prostate cancer severity. Additionally, SEMA3C has been shown to be upregulated in response to chemotherapy and radiation treatment, promote metastasis to the lung, and promote tumourigenicity of glioma cells. SEMA3C has also been documented to increase cell proliferation and migration, decrease apoptosis, and promote integrin signaling and VEGF secretion in endothelial cells. SEMA3C was shown to drive migration of breast cancer cells and recent studies have highlighted the importance and prognostic value of SEMA3C in prostate cancer. Given SEMA3C's roles in development and its augmented expression in PCa, we hypothesized that SEMA3C promotes cancer progression by driving mesenchymal and stem-like phenotypes. Other class 3 semaphorins have been shown to drive EMT and the link between SEMA3C and stemness has been established in glioma cells. In the present study, using gain of function studies coupled to gene expression (qPCR, Western blot, FACS, immunofluorescence microscopy) and functional studies (migration, invasion, and sphere-forming assays) we show that ectopic expression of SEMA3C in RWPE-1, a normal prostate epithelial cell line, promotes epithelial-to-mesenchymal transition and stemness. Specifically, we find that overexpression of SEMA3C leads to an upregulation of EMT markers and migratory and invasive phenotypes. SEMA3C overexpression was also associated with an upregulation of the cancer stem cell marker, CD44, and heightened sphere-forming capabilities. Additionally, using ultrasound-guided intracardiac injection of SEMA3C-overexpressing cells, we show that SEMA3C drives cell dissemination in vivo. We conclude from our studies that SEMA3C is a driver of prostate cancer by promoting epithelial-to-mesenchymal transition and stemness. Citation Format: Kevin J. Tam, Daniel H. Hui, Wilson C. Lee, Mingshu Dong, Tabitha Tombe, Ivy Z. Jiao, Shahram Khosravi, Ario Takeuchi, James W. Peacock, Larissa Ivanova, Igor Moskalev, Martin E. Gleave, Ralph Buttyan, Michael E. Cox, Christopher J. Ong. Semaphorin 3C drives invasiveness in prostate cells through epithelial-to-mesenchymal transition and stemness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1087.
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) | 0.003 | 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".