ArticleThe Journal of clinical investigation2014
Pancreatic cancer-associated retinoblastoma 1 dysfunction enables TGF-β to promote proliferation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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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.
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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.
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Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
- TGF-β Induced by Allergic Lung Inflammation Enhances Os-Teosarcoma Lung Metastasis in a Mouse Comorbidity Model.International journal of molecular sciences · 2025Article
- Unleashing Wnts: Wnt Ligands Fuel Cancer Spread.Journal of cancer biology · 2025Article
- PDCD10 promotes the tumor-supporting functions of TGF-β in pancreatic cancer.Clinical science (London, England : 1979) · 2024Article
- The pRb/RBL2-E2F1/4-GCN5 axis regulates cancer stem cell formation and G0 phase entry/exit by paracrine mechanisms.Nature communications · 2024Article
- Investigating underlying molecular mechanisms, signaling pathways, emerging therapeutic approaches in pancreatic cancer.Frontiers in oncology · 2024Review
- Prognostic role of IRS-4 in the survival of patients with pancreatic cancer.Histology and histopathology · 2022Article
- Berberine Suppresses Lung Metastasis of CancerFrontiers in pharmacology · 2022Article
- Cell-free DNA TAPS provides multimodal information for early cancer detection.Science advances · 2021Article
- Article
- The Role of TGF-Evidence-based complementary and alternative medicine : eCAM · 2021Review
- MiR-146b-3p regulates proliferation of pancreatic cancer cells with stem cell-like properties by targeting MAP3K10.Journal of Cancer · 2021Article
- Effect of miR-215 on the Expression of Tumor Suppressor Gene Rb1 in Retinoblastoma Cell Lines.Iranian journal of public health · 2020Article
- Identification of a Ubiquitination-Related Gene Risk Model for Predicting Survival in Patients With Pancreatic Cancer.Frontiers in genetics · 2020Article
- Effect of combined propofol-sevoflurane anesthesia on immune function in pediatric patients with acute lymphoblastic leukemia.Oncology letters · 2019Article
- Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition.Nature communications · 2019Article
- The Role of TGF-β and Its Receptors in Gastrointestinal Cancers.Translational oncology · 2019Review
- Notch signaling via regulation of RB and p-AKT but not PIK3CG contributes to MIA PaCa-2 cell growth and migration to affect pancreatic carcinogenesis.Oncology letters · 2018Article
- Downregulation of Human Endogenous Retrovirus Type K (HERV-K) ViralClinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- The pancreatic cancer microenvironment: A true double agent.Journal of surgical oncology · 2017Review
- TGF-β1 signaling pathway serves a role in HepG2 cell regulation by affecting the protein expression of PCNA, gankyrin, p115, XIAP and survivin.Oncology letters · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is often associated with overexpression of TGF-β. Given its tumor suppressor functions, it is unclear whether TGF-β is a valid therapeutic target for PDAC. Here, we found that proliferating pancreatic cancer cells (PCCs) from human PDAC patients and multiple murine models of PDAC (mPDAC) often exhibit abundant levels of phosphorylated retinoblastoma 1 (RB) and Smad2. TGF-β1 treatment enhanced proliferation of PCCs isolated from KrasG12D-driven mPDAC that lacked RB (KRC cells). This mitogenic effect was abrogated by pharmacological inhibition of type I TGF-β receptor kinase, combined inhibition of MEK/Src or MEK/PI3K, and restoration of RB expression. TGF-β1 promoted epithelial-to-mesenchymal transition (EMT), invasion, Smad2/3 phosphorylation, Src activation, Wnt reporter activity, and Smad-dependent upregulation of Wnt7b in KRC cells. Importantly, TGF-β1-induced mitogenesis was markedly attenuated by inhibition of Wnt secretion. In an in vivo syngeneic orthotopic model, inhibition of TGF-β signaling suppressed KRC cell proliferation, tumor growth, stroma formation, EMT, metastasis, ascites formation, and Wnt7b expression, and markedly prolonged survival. Together, these data indicate that RB dysfunction converts TGF-β to a mitogen that activates known oncogenic signaling pathways and upregulates Wnt7b, which synergize to promote PCC invasion, survival, and mitogenesis. Furthermore, this study suggests that concomitantly targeting TGF-β and Wnt7b signaling in PDAC may disrupt these aberrant pathways, which warrants further evaluation in preclinical models.
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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.