Abstract 1973: Caveolin-1 promotes cell proliferation, EGFR activation and tumor growth in kidney cancer
Bibliographic record
Abstract
Abstract Tumor hypoxia is associated with disease progression, drug resistance and poor prognosis. It has been shown previously that hypoxia prolongs the activation of epidermal growth factor receptor (EGFR) by delaying clathrin-dependent endocytosis-mediated deactivation of receptors. Recently, caveolin (CAV) mediated signaling and trafficking have been reported to be involved in the oncogenesis of many tumours, including clear cell renal cell carcinoma (CCRCC). However, the role of CAV-1 in the tumor progression is unclear. Here, we show that the loss of von Hippel-Lindau (VHL) protein – the principal negative regulator of hypoxia-inducible factor (HIF) – increases the auto-phosphorylation of epidermal growth factor receptor (EGFR), thus attributing to an enhanced ligand-independent cell signaling pathway, majorly Ras-Raf-MEK-ERK pathway, and leading to cell proliferation. The auto-phosphorylation of EGFR is due to the HIF-dependent overexpression of caveolin-1 (CAV-1) at the level of transcription, which enhances the association between EGFR and CAV-1 and the auto-dimerization of EGFR. Primary CCRCC tumors and numerous hypoxia treated tumor cell lines exhibit significantly higher expression of CAV-1 protein. Using a dorsal skin-fold window chamber on SCID mice, shCAV-1 knockdown 786-O tumor cell line exhibits lower growth than that of shscramble counterpart in xenografts. These findings support a model in which tumour hypoxia or oncogenic activation of HIF prolongs ligand-independent RTK signaling through the over-expression of CAV-1. Given the oncogenic role of CAV-1, it should be considered as a future therapeutic target in cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1973. doi:10.1158/1538-7445.AM2011-1973
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".