ArticleOncogene2017
TGFβ engages MEK/ERK to differentially regulate benign and malignant pancreas cell function.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 66 citations in OpenAlex.
- The multi-faceted roles of cancer-associated fibroblasts in pancreatic cancer.Cellular signalling · 2025Review
- TGF-β-Induced PAUF Plays a Pivotal Role in the Migration and Invasion of Human Pancreatic Ductal Adenocarcinoma Cell Line Panc-1.International journal of molecular sciences · 2024Article
- PDCD10 promotes the tumor-supporting functions of TGF-β in pancreatic cancer.Clinical science (London, England : 1979) · 2024Article
- AMP-activated protein kinase activation suppresses leptin expression independently of adipogenesis in primary murine adipocytes.The Biochemical journal · 2024Article
- Pterostilbene suppresses head and neck cancer cell proliferation via induction of apoptosis.Turkish journal of biology = Turk biyoloji dergisi · 2024Article
- Review
- The role of TGF-β in the tumor microenvironment of pancreatic cancer.Genes & diseases · 2023Review
- Personalized matched targeted therapy in advanced pancreatic cancer: a pilot cohort analysis.NPJ genomic medicine · 2023Article
- The difficulty in translating the preclinical success of combined TGFβ and immune checkpoint inhibition to clinical trial.EBioMedicine · 2022Review
- Diversification of PAR signaling through receptor crosstalk.Cellular & molecular biology letters · 2022Review
- DNA Polymerase Theta Plays a Critical Role in Pancreatic Cancer Development and Metastasis.Cancers · 2022Article
- Oncogenic Pathways in Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Early differential responses elicited by BRAFCell death & disease · 2022Article
- Loss of SMAD4 Is Associated With Poor Tumor Immunogenicity and Reduced PD-L1 Expression in Pancreatic Cancer.Frontiers in oncology · 2022Article
- TGFβ Signaling in the Pancreatic Tumor Microenvironment.Cancers · 2021Review
- Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model.Journal of translational medicine · 2021Article
- Chronic inflammation promotes epithelial-mesenchymal transition-mediated malignant phenotypes and lung injury in experimentally-induced pancreatitis.Life sciences · 2021Article
- Dynamic Stromal Alterations Influence Tumor-Stroma Crosstalk to Promote Pancreatic Cancer and Treatment Resistance.Cancers · 2021Review
- ROS and TGFβ: from pancreatic tumour growth to metastasis.Journal of experimental & clinical cancer research : CR · 2021Review
- Trials and tribulations of pancreatic cancer immunotherapy.Cancer letters · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While TGFβ signals are anti-proliferative in benign and well-differentiated pancreatic cells, TGFβ appears to promote the progression of advanced cancers. To better understand dysregulation of the TGFβ pathway, we first generated mouse models of neoplastic disease with TGFβ receptor deficiencies. These models displayed reduced levels of pERK irrespective of KRAS mutation. Furthermore, exogenous TGFβ led to rapid and sustained TGFBR1-dependent ERK phosphorylation in benign pancreatic duct cells. Similar to results that our group has published in colon cancer cells, inhibition of ERK phosphorylation in duct cells mitigated TGFβ-induced upregulation of growth suppressive pSMAD2 and p21, prevented downregulation of the pro-growth signal CDK2 and ablated TGFβ-induced EMT. These observations suggest that ERK is a key factor in growth suppressive TGFβ signals, yet may also contribute to detrimental TGFβ signaling such as EMT. In neoplastic PanIN cells, pERK was not necessary for either TGFβ-induced pSMAD2 phosphorylation or CDK2 repression, but was required for upregulation of p21 and EMT indicating a partial divergence between TGFβ and MEK/ERK in early carcinogenesis. In cancer cells, pERK had no effect on TGFβ-induced upregulation of pSMAD2 and p21, suggesting the two pathways have completely diverged with respect to the cell cycle. Furthermore, inhibition of pERK both reduced levels of CDK2 and prevented EMT independent of exogenous TGFβ, consistent with most observations identifying pERK as a tumor promoter. Combined, these data suggest that during carcinogenesis pERK initially facilitates and later antagonizes TGFβ-mediated cell cycle arrest, yet remains critical for the pathological, EMT-inducing arm of TGFβ signaling.
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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.