ArticleCell death & disease2011
Novel tumor suppressive function of Smad4 in serum starvation-induced cell death through PAK1-PUMA pathway.
Article in Cell death & disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Combined BCL-2 and PI3K/AKT Pathway Inhibition inInternational journal of molecular sciences · 2023Article
- The role of P53 up-regulated modulator of apoptosis (PUMA) in ovarian development, cardiovascular and neurodegenerative diseases.Apoptosis : an international journal on programmed cell death · 2021Review
- Aberrant activation of the CD45-Wnt signaling axis promotes stemness and therapy resistance in colorectal cancer cells.Theranostics · 2021Article
- Copanlisib promotes growth inhibition and apoptosis by modulating the AKT/FoxO3a/PUMA axis in colorectal cancer.Cell death & disease · 2020Article
- JAK/STAT and VEGF/PAK1 signaling as emerging targets for topical treatment of psoriasis: a pilot study.International journal of clinical and experimental pathology · 2020Article
- Anti-cancer effect of novel PAK1 inhibitor via induction of PUMA-mediated cell death and p21-mediated cell cycle arrest.Oncotarget · 2017Article
- The guanine nucleotide exchange factor Net1 facilitates the specification of dorsal cell fates in zebrafish embryos by promoting maternal β-catenin activation.Cell research · 2017Article
- Review
- p21-Activated Kinase 4 (PAK4) as a Predictive Marker of Gemcitabine Sensitivity in Pancreatic Cancer Cell Lines.Cancer research and treatment · 2015Article
- Clinicopathological and cellular signature of PAK1 in human bladder cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Central role of SIAH inhibition in DCC-dependent cardioprotection provoked by netrin-1/NO.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
- Genetic targeting of B-RafV600E affects survival and proliferation and identifies selective agents against BRAF-mutant colorectal cancer cells.Molecular cancer · 2014Article
- Asymmetric dimethylarginine attenuates serum starvation-induced apoptosis via suppression of the Fas (APO-1/CD95)/JNK (SAPK) pathway.Cell death & disease · 2013Article
- Genetic disruption of Abl nuclear import reduces renal apoptosis in a mouse model of cisplatin-induced nephrotoxicity.Cell death and differentiation · 2013Article
- The impact of TGF-β1 on the mRNA expression of TβR I, TβR II, Smad4 and the invasiveness of the JEG-3 placental choriocarcinoma cell line.Oncology letters · 2012Article
- Review
- PAK signaling in cancer.Cellular logistics · 2012Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DPC4 (deleted in pancreatic cancer 4)/Smad4 is an essential factor in transforming growth factor (TGF)-β signaling and is also known as a frequently mutated tumor suppressor gene in human pancreatic and colon cancer. However, considering the fact that TGF-β can contribute to cancer progression through transcriptional target genes, such as Snail, MMPs, and epithelial-mesenchymal transition (EMT)-related genes, loss of Smad4 in human cancer would be required for obtaining the TGF-β signaling-independent advantage, which should be essential for cancer cell survival. Here, we provide the evidences about novel role of Smad4, serum-deprivation-induced apoptosis. Elimination of serum can obviously increase the Smad4 expression and induces the cell death by p53-independent PUMA induction. Instead, Smad4-deficient cells show the resistance to serum starvation. Induced Smad4 suppresses the PAK1, which promotes the PUMA destabilization. We also found that Siah-1 and pVHL are involved in PAK1 destabilization and PUMA stabilization. In fact, Smad4-expressed cancer tissues not only show the elevated expression of PAK1, but also support our hypothesis that Smad4 induces PUMA-mediated cell death through PAK1 suppression. Our results strongly suggest that loss of Smad4 renders the resistance to serum-deprivation-induced cell death, which is the TGF-β-independent tumor suppressive role of Smad4.
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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.