ArticleCancer research2012
In vivo regulation of TGF-β by R-Ras2 revealed through loss of the RasGAP protein NF1.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- KRAS is required for plexiform neurofibroma formation and represents a targetable vulnerability in established tumors.Science advances · 2026Article
- NF1 and SPRED1/2 cooperate through RAS-MAPK-independent functions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Active R-RAS2/TC21 prevents cell cycle arrest and morphological alterations in mouse embryonic fibroblasts lacking RAS proteins.Oncogene · 2025Article
- TGFβ-dependent signaling drives tumor growth and aberrant extracellular matrix dynamics in NF1-associated plexiform neurofibroma.Science advances · 2025Article
- MEK-SHP2 inhibition prevents tibial pseudarthrosis caused byScience translational medicine · 2024Article
- Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors.Frontiers in immunology · 2024Article
- RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights.The Journal of investigative dermatology · 2023Review
- Basement membrane proteins in extracellular matrix characterize NF1 neurofibroma development and response to MEK inhibitor.The Journal of clinical investigation · 2023Article
- Article
- Systemic Options for Malignant Peripheral Nerve Sheath Tumors.Current treatment options in oncology · 2021Review
- Autocrine TGF-β in Cancer: Review of the Literature and Caveats in Experimental Analysis.International journal of molecular sciences · 2021Review
- AfterNeuro-oncology advances · 2020Review
- Diagnosis and management of malignant peripheral nerve sheath tumors: Current practice and future perspectives.Neuro-oncology advances · 2020Review
- Schwann cells support oncogenic potential of pancreatic cancer cells through TGFβ signaling.Cell death & disease · 2019Article
- Article
- An inflammatory gene signature distinguishes neurofibroma Schwann cells and macrophages from cells in the normal peripheral nervous system.Scientific reports · 2017Article
- The genomic landscape of juvenile myelomonocytic leukemia.Nature genetics · 2015Article
- A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor.Nature reviews. Cancer · 2015Review
- Structure and decay of a proto-Y region in Tilapia, Oreochromis niloticus.BMC genomics · 2014Article
- Brain tumors in Neurofibromatosis type 1.Neuro-oncology advancesReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Ras superfamily proteins participate in TGF-β-mediated developmental pathways that promote either tumor suppression or progression. However, the specific Ras proteins, which integrate in vivo with TGF-β signaling pathways, are unknown. As a general approach to this question, we activated all Ras proteins in vivo by genetic deletion of the RasGAP protein Nf1 and examined mice doubly deficient in a Ras protein to determine its requirement in formation of TGF-β-dependent neurofibromas that arise in Nf1-deficient mice. Animals lacking Nf1 and the Ras-related protein R-Ras2/TC21 displayed a delay in formation of neurofibromas but an acceleration in formation of brain tumors and sarcomas. Loss of R-Ras2 was associated with elevated expression of TGF-β in Nf1-deficient Schwann cell precursors, blockade of a Nf1/TGFβRII/AKT-dependent autocrine survival loop in tumor precursor cells, and decreased precursor cell numbers. Furthermore, the increase in size of sarcomas from xenografts doubly deficient in these genes was also found to be TGF-β-dependent, in this case resulting from cell nonautonomous effects on endothelial cells and myofibroblasts. Extending these findings in clinical specimens, we documented an increase in TGF-β ligands and an absence of TGF-β receptor II in malignant peripheral nerve sheath tumors, which correspond to tumors in the Nf1-deficient mouse model. Together, our findings reveal R-Ras2 as a critical regulator of TGF-β signaling in vivo.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.