ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2008
TGF-beta mediates PTEN suppression and cell motility through calcium-dependent PKC-alpha activation in pancreatic cancer cells.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 68 citations in OpenAlex.
- PTEN status on gonadotropin-releasing hormone (GnRH) metabolite, GnRH-(1-5), effects in endometrial cancer cell lines migration, & transcriptomic analysis of basal cell line and tumor gene expressions†.Biology of reproduction · 2025Article
- PAI-1 mediates TGF-β1-induced myofibroblast activation in tenocytes via mTOR signaling.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines.International journal of molecular sciences · 2023Article
- The role of extended synaptotagmin at membrane contact sites in cancer research.Frontiers in cell and developmental biology · 2023Review
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- Novel Soy Peptide CBP: Stimulation of Osteoblast Differentiation via TβRI-p38-MAPK-Depending RUNX2 Activation.Nutrients · 2022Article
- Orai1 Channel Regulates Human-Activated Pancreatic Stellate Cell Proliferation and TGFCancers · 2021Article
- Role of the TRP Channels in Pancreatic Ductal Adenocarcinoma Development and Progression.Cells · 2021Review
- Alterations of PTEN and SMAD4 methylation in diagnosis of breast cancer: implications of methyl II PCR assay.Journal, genetic engineering & biotechnology · 2021Article
- The Aurora kinase/β-catenin axis contributes to dexamethasone resistance in leukemia.NPJ precision oncology · 2021Article
- Review
- Ion Channel Signature in Healthy Pancreas and Pancreatic Ductal Adenocarcinoma.Frontiers in pharmacology · 2020Review
- Protein kinase Cα-mediated phosphorylation of Twist1 at Ser-144 prevents Twist1 ubiquitination and stabilizes it.The Journal of biological chemistry · 2019Article
- Regulation and modulation of PTEN activity.Molecular biology reports · 2018Review
- Review
- GDF11 Modulates CaInternational journal of molecular sciences · 2018Article
- Protein kinase C isoforms in the normal pancreas and in pancreatic disease.Cellular signalling · 2017Review
- TGF-β induces phosphorylation of phosphatase and tensin homolog: implications for fibrosis of the trabecular meshwork tissue in glaucoma.Scientific reports · 2017Article
- Article
- Targeting protein kinase C subtypes in pancreatic cancer.Expert review of anticancer therapy · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Transforming growth factor-beta (TGF-beta) suppresses growth via the TGF-beta-SMAD pathway but promotes growth in cancer cells with disrupted SMAD signaling and corresponds to an invasive phenotype. TGF-beta also downregulates the tumor suppressor PTEN that is rarely mutated in sporadic pancreatic cancer; this downregulation may mediate cell proliferation and invasiveness, but the mechanism is unknown. Here, we examined whether TGF-beta modulation of PTEN was mediated by protein kinase C (PKC). We have previously demonstrated that SMAD4-null BxPc-3 pancreatic cancer cells treated with TGF-beta1 (10 ng/ml) suppressed PTEN expression and increased cell proliferation. TGF-beta-treated cells were examined for PKC activation and its coupling to PTEN expression, utilizing pharmacological and knockdown methods. Calcium mobilization and cell migration were also examined. In BxPc-3 cells, only two PKC isoforms were activated by TGF-beta, and PTEN downregulation by TGF-beta was specifically mediated by PKC-alpha. In parallel, TGF-beta rapidly induced an increase in cytoplasmic free calcium from intracellular stores, consistent with subsequent PKC-alpha activation. The TGF-beta-induced increase in cell migration was blocked by knockdown of PKC-alpha. Thus calcium-dependent PKC-alpha mediates TGF-beta-induced transcriptional downregulation of PTEN, and this pathway promotes cell migration in a SMAD4-null environment. The TGF-beta-PKC-alpha-PTEN cascade may be a key pathway for pancreatic cancer cells to proliferate and metastasize.
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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.