ArticleOncotarget2013
Efemp1 and p27(Kip1) modulate responsiveness of pancreatic cancer cells towards a dual PI3K/mTOR inhibitor in preclinical models.
Article in Oncotarget, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Molecular signaling in pancreatic ductal metaplasia: emerging biomarkers for detection and intervention of early pancreatic cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- HDAC2 Facilitates Pancreatic Cancer Metastasis.Cancer research · 2022Article
- Genetic Screens Identify a Context-Specific PI3K/p27Kip1 Node Driving Extrahepatic Biliary Cancer.Cancer discovery · 2021Article
- Chemical composition of cold-pressed blackberry seed flour extract and its potential health-beneficial properties.Food science & nutrition · 2020Article
- Effects of RNAi-induced Skp2 inhibition on cell cycle, apoptosis and proliferation of endometrial carcinoma cells.Experimental and therapeutic medicine · 2019Article
- MTOR inhibitor-based combination therapies for pancreatic cancer.British journal of cancer · 2018Article
- Preprogramming therapeutic response of PI3K/mTOR dual inhibitor via the regulation of EHMT2 and p27 in pancreatic cancer.American journal of cancer research · 2018Article
- E47 Governs the MYC-CDKN1B/p27Cellular and molecular gastroenterology and hepatology · 2018Article
- Loss of p27Kip¹ promotes metaplasia in the pancreas via the regulation of Sox9 expression.Oncotarget · 2015Article
- Toward rapamycin analog (rapalog)-based precision cancer therapy.Acta pharmacologica Sinica · 2015Review
- Targeted Inhibition of Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Sensitizes Pancreatic Cancer Cells to Doxorubicin without Exacerbating Cardiac Toxicity.Molecular pharmacology · 2015Article
- Inhibition of DNA methyltransferase as a novel therapeutic strategy to overcome acquired resistance to dual PI3K/mTOR inhibitors.Oncotarget · 2015Article
- Gerosuppression in confluent cells.Aging · 2014Article
- A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer.Nature medicine · 2014Article
- Article
- Targeting nucleocytoplasmic transport in cancer therapy.Oncotarget · 2014Review
- MYC and EGR1 synergize to trigger tumor cell death by controlling NOXA and BIM transcription upon treatment with the proteasome inhibitor bortezomib.Nucleic acids research · 2014Article
- PCTAIRE1 regulates p27 stability, apoptosis and tumor growth in malignant melanoma.Oncoscience · 2014Article
- Quo vadis, Kras?Oncotarget · 2013Article
- Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease with a poor prognosis and targeted therapies have failed in the clinic so far. Several evidences point to the phosphatidylinositol 3-kinase (PI3K)-mTOR pathway as a promising signaling node for targeted therapeutic intervention. Markers, which predict responsiveness of PDAC cells towards PI3K inhibitors are unknown. However, such markers are needed and critical to better stratify patients in clinical trials. We used a large murine Kras(G12D)- and PI3K (p110α(H1047R))-driven PDAC cell line platform to unbiased define modulators of responsiveness towards the dual PI3K-mTOR inhibitor Bez235. In contrast to other tumor models, we show that Kras(G12D)- and PI3K (p110α(H1047R))-driven PDAC cell lines are equally sensitive towards Bez235. In an unbiased approach we found that the extracellular matrix protein Efemp1 controls sensitivity of murine PDAC cells towards Bez235. We show that Efemp1 expression is connected to the cyclin-dependent kinase inhibitor p27(Kip1). In a murine Kras(G12D)-driven PDAC model, p27(Kip1) haploinsufficiency accelerates cancer development in vivo. Furthermore, p27(Kip1) controls Bez235 sensitivity in a gene dose-dependent fashion in murine PDAC cells and lowering of p27(Kip1) decreases Bez235 responsiveness in murine PDAC models. Together, we define the Efemp1-p27(Kip1) axis as a potential marker module of PDAC cell sensitivity towards dual PI3K-mTOR inhibitors, which might help to better stratify patients in clinical trials.
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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.