HCaRG/COMMD5 inhibits ErbB receptor-driven renal cell carcinoma
Bibliographic record
Abstract
// Hiroyuki Matsuda 1, 2, 3 , Carole G. Campion 1 , Kyoko Fujiwara 3 , Jin Ikeda 3 , Suzanne Cossette 1 , Thomas Verissimo 1 , Maiko Ogasawara 3 , Louis Gaboury 4, 5 , Kosuke Saito 3 , Kenya Yamaguchi 6 , Satoru Takahashi 6 , Morito Endo 7 , Noboru Fukuda 8 , Masayoshi Soma 3 , Pavel Hamet 1, 2 and Johanne Tremblay 1, 2 1 Centre de recherche, Centre hospitalier de l’Université de Montréal (CRCHUM), Montréal, Québec, Canada, H2X 0A9 2 Department of Medicine, Université de Montréal, Montréal, Québec, Canada, H3T 1J4 3 Division of General Medicine, Department of Internal Medicine, Nihon University, Itabashi-ku, Tokyo, Japan, 173-8610 4 Institut de Recherche en Immunologie et Cancérologie (IRIC), Université de Montréal, Pavillon Marcelle-Coutu, Québec, Canada, H3T 1J4 5 Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec, Canada, H3T 1J4 6 Department of Urology, Nihon University, Itabashi-ku, Tokyo, Japan, 173-8610 7 Faculty of Human Health Science, Hachinohe Gakuin University, Hachinohe, Aomori, Japan, 031-8588 8 University Research Center, Nihon University, Chiyoda-ku, Tokyo, Japan, 102-8251 Correspondence to: Johanne Tremblay, email: johanne.tremblay@umontreal.ca Keywords: HCaRG/COMMD5, renal cell carcinoma, EGFR, differentiation, autophagic cell death Received: March 10, 2017 Accepted: May 08, 2017 Published: May 19, 2017 ABSTRACT Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is highly expressed in renal proximal tubules, where it contributes to the control of cell proliferation and differentiation. HCaRG accelerates tubular repair by facilitating re-differentiation of injured proximal tubular epithelial cells, thus improving mouse survival after acute kidney injury. Sustained hyper-proliferation and de-differentiation are important hallmarks of tumor progression. Here, we demonstrate that cancer cells overexpressing HCaRG maintain a more differentiated phenotype, while several of them undergo autophagic cell death. Its overexpression in mouse renal cell carcinomas led to smaller tumor size with less tumor vascularization in a homograft tumor model. Mechanistically, HCaRG promotes de-phosphorylation of the proto-oncogene erythroblastosis oncogene B (ErbB)2/HER2 and epigenetic gene silencing of epidermal growth factor receptor and ErbB3 via promoter methylation. Extracellular signal-regulated kinase, AKT and mammalian target of rapamycin which mediate ErbB-dowstream signaling pathways are inactivated by HCaRG expression. In addition, HCaRG is underexpressed in human renal cell carcinomas and more expressed in normal tissue adjacent to renal cell carcinomas of patients with favorable prognosis. Taken together, our data suggest a role for HCaRG in the inhibition of tumor progression as a natural inhibitor of the ErbB signals in cancer and as a potential prognostic marker for renal cell carcinomas.
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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".