ReviewCarcinogenesis2011
Smad phosphoisoform signaling specificity: the right place at the right time.
Review in Carcinogenesis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
What it found
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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
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- The Activation Status of the TGF-β Transducer Smad2 Is Associated with a Reduced Survival in Gastrointestinal Cancers: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2019Pooled it
- Acute normobaric hypoxia blunts contraction-mediated mTORC1- and JNK-signaling in human skeletal muscle.Acta physiologica (Oxford, England) · 2022Trial
- Targeting androgen receptor as a novel radiosensitizing therapy to improve long-term survival and anti-tumor immunity in glioblastoma via TGF-β/Smad3 Axis reprogramming.Cell death discovery · 2026Article
- C-MYC as a key effector of WNT, PI3K/AKT, MAPK, and TGF-β signaling pathways in regulation of epithelial-mesenchymal transition during tumor metastasis.Cancer cell international · 2026Review
- Proline promotes prolyl 4-hydroxylase subunit alpha 1 via transforming growth factor beta 1 to increase the synthesis and deposition of collagen in grass carp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Targeting Androgen Receptor as a Novel Radiosensitizing Therapy to Improve Long-Term Survival and Anti-tumor Immunity in Glioblastoma via TGF-β/Smad3 Axis Reprogramming.Research square · 2026Article
- Porphyromonas gingivalis Type 9 Secretion System Promotes Dysregulation of Vascular Smooth Muscle Cell Plasticity With Perturbed TGF-β/Smad Signaling.MicrobiologyOpen · 2025Article
- Eosinophils-Induced Lumican Secretion by Synovial Fibroblasts Alleviates Cartilage Degradation via the TGF-β Pathway Mediated by Anxa1 Binding.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Signaling molecules in the microenvironment of hepatocellular carcinoma.Functional & integrative genomics · 2024Review
- TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy.Human reproduction update · 2024Review
- Differential Smad2/3 linker phosphorylation is a crosstalk mechanism of Rho/ROCK and canonical TGF-β3 signaling in tenogenic differentiation.Scientific reports · 2024Article
- Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Ubiquitination Process Mediates Prostate Cancer Development and Metastasis through Multiple Mechanisms.Cell biochemistry and biophysics · 2024Review
- The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis.International journal of biological sciences · 2024Review
- Hepatitis B virus X protein and TGF-β: partners in the carcinogenic journey of hepatocellular carcinoma.Frontiers in oncology · 2024Review
- TGF-β/Smads signaling pathway, Hippo-YAP/TAZ signaling pathway, and VEGF: Their mechanisms and roles in vascular remodeling related diseases.Immunity, inflammation and disease · 2023Review
- Smad3 Phospho-Isoform Signaling in Nonalcoholic Steatohepatitis.International journal of molecular sciences · 2022Review
- Activin A promotes cell proliferation, invasion and migration and predicts poor prognosis in patients with colorectal cancer.Oncology reports · 2022Article
- TGF-β1-induced RAP2 regulates invasion in pancreatic cancer.Acta biochimica et biophysica Sinica · 2022Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor (TGF)-β antagonizes mitogenic Ras signaling during epithelial regeneration, but TGF-β and Ras act synergistically in driving tumor progression. Insights into these apparently contradictory effects have come from recent detailed analyses of the TGF-β signaling process. Here, we summarize the different modes of TGF-β/Ras signaling in normal epithelium and neoplasms and show how perturbation of TGF-β signaling by Ras may contribute to a shift from tumor-suppressive to protumorigenic TGF-β activity during tumor progression. Smad proteins, which convey signals from TGF-β receptors to the nucleus, have intermediate linker regions between conserved Mad homology (MH) 1 and MH2 domains. TGF-β Type I receptor and Ras-associated kinases differentially phosphorylate Smad2 and Smad3 to create C-terminally (C), linker (L) or dually (L/C) phosphorylated (p) isoforms. In epithelial homeostasis, TGF-β-mediated pSmad3C signaling opposes proliferative responses induced by mitogenic signals. During carcinogenesis, activation of cytoplasmic Ras-associated kinases including mitogen-activated protein kinase confers a selective advantage on benign tumors by shifting Smad3 signaling from a tumor-suppressive pSmad3C to an oncogenic pSmad3L pathway, leading to carcinoma in situ. Finally, at the edges of advanced carcinomas invading adjacent tissues, nuclear Ras-associated kinases such as cyclin-dependent kinases, together with cytoplasmic kinases, alter TGF-β signals to more invasive and proliferative pSmad2L/C and pSmad3L/C signaling. Taken together, TGF-β signaling specificity arises from spatiotemporal dynamics of Smad phosphoisoforms. Based on these findings, we have reason to hope that pharmacologic inhibition of linker phosphorylation might suppress progression to human advanced carcinomas by switching from protumorigenic to tumor-suppressive TGF-β signaling.
Indexed as
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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.