ArticleCell death and differentiation2012
Src tyrosine kinase inhibits apoptosis through the Erk1/2- dependent degradation of the death accelerator Bik.
Article in Cell death and differentiation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
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- Exploring the effect of Huangqi Fuling Decoction on gastric cancer based on UPLC-MS, network pharmacology and experiments in vitro.BMC complementary medicine and therapies · 2025Article
- A new era in cancer therapy: targeting the Proteasome-Bcl-2 axis.Journal of experimental & clinical cancer research : CR · 2025Review
- Anti-tumor activity of beauvericin: focus on intracellular signaling pathways.Mycotoxin research · 2024Review
- Secretion of Sphinganine by Drug-Induced Cancer Cells and Modified Mimetic Sphinganine (MMS) as c-Src Kinase Inhibitor.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Molecular determinants of etoposide resistance in HL60 cells.Bioinformation · 2022Article
- Autophagy Inhibition in BRAF-Driven Cancers.Cancers · 2021Review
- Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020Review
- ERK signalling: a master regulator of cell behaviour, life and fate.Nature reviews. Molecular cell biology · 2020Review
- c-Src kinase impairs the expression of mitochondrial OXPHOS complexes in liver cancer.Cellular signalling · 2020Article
- Regulation of Src Family Kinases during Colorectal Cancer Development and Its Clinical Implications.Cancers · 2020Review
- Rho guanine nucleotide exchange factor ARHGEF10 is a putative tumor suppressor in pancreatic ductal adenocarcinoma.Oncogene · 2020Article
- Targeting melanoma's MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors.Nature communications · 2019Article
- Identification of biomarkers and their functions in dasatinib-resistant pancreatic cancer using bioinformatics analysis.Oncology letters · 2019Article
- Article
- Kinome-Wide siRNA Screening Identifies Src-Enhanced Resistance of Chemotherapeutic Drugs in Triple-Negative Breast Cancer Cells.Frontiers in pharmacology · 2018Article
- Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling.The FEBS journal · 2017Review
- Proteasome Stress Triggers Death of SH-SY5Y and T98G Cells via Different Cellular Mechanisms.Neurochemical research · 2017Article
- Alpha 2 NaScientific reports · 2017Article
- Src Acts as an Effector for Ku70-dependent Suppression of Apoptosis through Phosphorylation of Ku70 at Tyr-530.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Src, the canonical member of the non-receptor family of tyrosine kinases, is deregulated in numerous cancers, including colon and breast cancers. In addition to its effects on cell proliferation and motility, Src is often considered as an inhibitor of apoptosis, although this remains controversial. Thus, whether the ability of Src to generate malignancies relies on an intrinsic aptitude to inhibit apoptosis or requires preexistent resistance to apoptosis remains somewhat elusive. Here, using mouse fibroblasts transformed with v-Src as a model, we show that the observed Src-dependent resistance to cell death relies on Src ability to inhibit the mitochondrial pathway of apoptosis by specifically increasing the degradation rate of the BH3-only protein Bik. This effect relies on the activation of the Ras-Raf-Mek1/2-Erk1/2 pathway, and on the phosphorylation of Bik on Thr124, driving Bik ubiquitylation on Lys33 and subsequent degradation by the proteasome. Importantly, in a set of human cancer cells with Src-, Kras- or BRAF-dependent activation of Erk1/2, resistances to staurosporine or thapsigargin were also shown to depend on Bik degradation rate via a similar mechanism. These results suggest that Bik could be a rate-limiting factor for apoptosis induction of tumor cells exhibiting deregulated Erk1/2 signaling, which may provide new opportunities for cancer therapies.
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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.