ArticleCell communication and signaling : CCS2026
SHP2 negatively regulates TGF-β signaling by destabilizing the TGF-β type I receptor.
Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSRC homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), acting as a central node of many signaling pathways, has an emerging role in many diseases, including cancer. Transforming growth factor β (TGF-β) affects a wide spectrum of biological processes, including cell proliferation, apoptosis, differentiation and migration, during embryonic development and oncogenesis. TGF-β regulates cell proliferation in a cell-context-dependent manner; loss of TGF-β-mediated growth inhibition is a major characteristic of cancer cells. SHP2 regulates canonical and non-canonical TGF-β signaling in cancer cells and fibroblasts, however, the mechanism by which TGF-β activates SHP2 and the role of SHP2 in TGF-β-mediated growth inhibition has remained unclear.
methodsThe phosphorylation and activation of SHP2 was assessed after TGF-β stimulation of normal and breast cancer cells. The interaction between SHP2 and SRC was determined by co-immunoprecipitation (co-IP) assay. Pharmacological inhibition and gRNA-mediated knockout were applied to assess the role of SHP2 in TGF-β signaling, and RNA-sequencing to identify gene expression patterns in SHP2 knockout cells treated with TGF-β. Functional studies were performed using breast cancer cells to validate the role of SHP2 in TGF-β -mediated growth inhibition.
resultsWe report that TGF-β activated SHP2 by promoting its tyrosine phosphorylation by SRC. SHP2 depletion in breast cancer cells reduced ubiquitination and degradation of TβRI by impeding the interaction between TβRI and SMAD7, which is a negative regulator of TβRI. Pharmacological or genetic inhibition of SHP2 facilitated TGF-β-induced SMAD2 phosphorylation and transcriptional responses. Consequently, inhibition of SHP2 profoundly enhanced TGF-β-induced cell growth arrest and senescence, including promotion of TGF-β-induced expression of the cell cycle inhibitor p15 at both gene and protein level.
conclusionsOur findings uncover a mechanism by which SHP2 is activated by TGF-β in a SRC-dependent manner, and functions in a negative feedback mechanism to regulate TGF-β signaling.
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.