Abstract 4994: RET isoforms differentially contribute to focal adhesion formation
Bibliographic record
Abstract
Abstract RET is a receptor tyrosine kinase crucial for the development of the kidney, and some neuroendocrine tissues. RET activation by its ligand, glial cell-line derived neurotrophic factor (GDNF), results in autophosphorylation of several key tyrosine kinase residues in the intracellular region, which allow binding of adaptor and signalling proteins, and consequently activation of various cellular processes, including survival, proliferation and migration. RET has two major protein isoforms, called RET9 and RET51 after the number of unique amino acids at the C-terminus, generated by alternative splicing. Although the RET isoforms are highly conserved across species, and both isoforms are normally co-expressed, they have major molecular and functional differences, including different transforming abilities, and trafficking properties. RET is implicated in several human diseases. Gain-of-function RET mutations result in the cancer syndrome multiple endocrine neoplasia type 2, that affects neuroendocrine tissues, somatic RET rearrangements are found in papillary thyroid carcinoma, and lung adenocarcinoma, and aberrant wild-type RET activation occurs in many cancers, including breast and pancreatic cancer. Focal adhesion protein complexes are involved in interactions of cells with the extracellular matrix, and are crucial for controlling cancer-related processes, including cell migration and invasion. The contributions of RET isoforms to the processes of focal adhesion formation and dynamics have not yet been investigated. To explore the roles of RET isoforms in focal adhesion formation, we used total internal resonance fluorescence (TIRF) microscopy to assess localization of various focal adhesion proteins, including paxillin, vinculin and zyxin in response to GDNF in a cell-based model system. Our results suggest that RET51 promotes more early (ie. paxillin) and late (ie. zyxin) stage focal adhesion formation than does RET9. Additionally, we demonstrate that the kinase dead form of RET51 results in a decrease of the number of focal adhesions compared to RET51 wild-type, suggesting that the increase in focal adhesion formation in the presence of RET51 is phosphorylation-dependent. Inhibition of SRC and FAK led to a reduction in focal adhesion formation, indicating that these pathways play roles in this process. Ongoing studies are investigating the focal adhesion dynamics of the RET isoforms and further characterizing the molecular differences underlying the ability of RET51 to induce greater focal adhesion formation than RET9. Citation Format: Piriya Yoganathan, Eric Lian, Lois M. Mulligan. RET isoforms differentially contribute to focal adhesion formation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4994. doi:10.1158/1538-7445.AM2015-4994
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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 | 0.000 | 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) | 0.004 | 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".