ArticleOncotarget2016
PHLPP negatively regulates cell motility through inhibition of Akt activity and integrin expression in pancreatic cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- PHLPP1 depletion promotes tumorigenesis and stemness in triple-negative breast cancer cells through AKT signaling.Medical oncology (Northwood, London, England) · 2025Article
- Emerging roles of PHLPP phosphatases in lung cancer.Frontiers in oncology · 2023Review
- Article
- Downregulation of PHLPP induced by endoplasmic reticulum stress promotes eIF2α phosphorylation and chemoresistance in colon cancer.Cell death & disease · 2021Article
- On the PHLPPside: Emerging roles of PHLPP phosphatases in the heart.Cellular signalling · 2021Review
- Emerging roles of PHLPP phosphatases in metabolism.BMB reports · 2021Review
- PHLPPing the balance: restoration of protein kinase C in cancer.The Biochemical journal · 2021Review
- miR-190-5p Alleviates Myocardial Ischemia-Reperfusion Injury by Targeting PHLPP1.Disease markers · 2021Article
- Inhibition of PHLPP1 ameliorates cardiac dysfunction via activation of the PI3K/Akt/mTOR signalling pathway in diabetic cardiomyopathy.Journal of cellular and molecular medicine · 2020Article
- Transcriptional Profiles of Skeletal Muscle Associated With Increasing Severity of White Striping in Commercial Broilers.Frontiers in physiology · 2020Article
- Identification of Potential Biomarkers with Diagnostic Value in Pituitary Adenomas Using Prediction Analysis for Microarrays Method.Journal of molecular neuroscience : MN · 2019Article
- Acute Physiology and Neurologic Outcomes after Brain Injury in SCOP/PHLPP1 KO Mice.Scientific reports · 2018Article
- SNORA74B gene silencing inhibits gallbladder cancer cells by inducing PHLPP and suppressing Akt/mTOR signaling.Oncotarget · 2017Article
- PHLPP regulates hexokinase 2-dependent glucose metabolism in colon cancer cells.Cell death discovery · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic adenocarcinoma is currently the fourth leading cause for cancer-related mortality. Malignant progression of pancreatic cancer depends not only on rapid proliferation of tumor cells but also on increased cell motility. In this study, we showed that increased PHLPP expression significantly reduced the rate of migration in pancreatic ductal adenocarcinoma (PDAC) cells whereas knockdown of PHLPP had the opposite effect. In addition, cell motility at the individual cell level was negatively regulated by PHLPP as determined using time-lapse imaging. Interestingly, the expression of β1 and β4 integrin proteins were decreased in PHLPP overexpressing cells and increased in PHLPP knockdown cells whereas the mRNA levels of integrin were not altered by changes in PHLPP expression. In determining the molecular mechanism underlying PHLPP-mediated regulation of integrin expression, we found that inhibition of lysosome activity rescued integrin expression in PHLPP overexpressing cells, thus suggesting that PHLPP negatively controls cell motility by inhibiting Akt activity to promote lysosome-dependent degradation of integrins. Functionally, the increased cell migration observed in PHLPP knockdown cells was effectively blocked by the neutralizing antibodies against β1 or β4 integrin. Taken together, our study identified a tumor suppressor role of PHLPP in suppressing cell motility by negatively regulating integrin expression in pancreatic cancer cells.
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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.