ArticleBiochimica et biophysica acta2016
Deoxycholic acid mediates non-canonical EGFR-MAPK activation through the induction of calcium signaling in colon cancer cells.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Cholecystectomy promotes the development of colorectal cancer by the alternation of bile acid metabolism and the gut microbiota.Frontiers in medicine · 2022Pooled it
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- Shaping death: how the microbiome regulates tumour cell demise and therapy response.Cancer metastasis reviews · 2026Review
- Multifaceted roles of microbiota-derived deoxycholic acid in gastrointestinal cancers: from barrier disruption to therapeutic implications.Human cell · 2025Review
- Deoxycholic acid induces reactive oxygen species accumulation and promotes colorectal cancer cell apoptosis through the CaMKII-CaWorld journal of gastrointestinal oncology · 2025Article
- Emerging role of bile acids in colorectal liver metastasis: From molecular mechanism to clinical significance (Review).International journal of oncology · 2025Review
- Microbiota-derived metabolites in tumorigenesis: mechanistic insights and therapeutic implications.Frontiers in pharmacology · 2025Review
- Obesity-Associated Colorectal Cancer.International journal of molecular sciences · 2024Review
- CaBiomolecules · 2023Review
- MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia.Cancer reports (Hoboken, N.J.) · 2023Article
- [Obesity and Colorectal Cancer].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2023Review
- Review
- Review
- Does postcholecystectomy increase the risk of colorectal cancer?Frontiers in microbiology · 2023Review
- Liver Steatosis and Steatohepatitis Alter Bile Acid Receptors in Brain and Induce Neuroinflammation: A Contribution of Circulating Bile Acids and Blood-Brain Barrier.International journal of molecular sciences · 2022Article
- Three-target treatment combined with surgery for BRAF V600E-mutant colon cancer with peritoneal metastasis: a case report.Journal of gastrointestinal oncology · 2022Article
- The role of bile acids in carcinogenesis.Cellular and molecular life sciences : CMLS · 2022Review
- Progress in the Study of Colorectal Cancer Caused by Altered Gut Microbiota After Cholecystectomy.Frontiers in endocrinology · 2022Review
- Secondary Bile Acids and Tumorigenesis in Colorectal Cancer.Frontiers in oncology · 2022Review
- The roles of microbial products in the development of colorectal cancer: a review.Bioengineered · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Obesity and a western diet have been linked to high levels of bile acids and the development of colon cancer. Specifically, increased levels of the bile acid deoxycholic acid (DCA), an established tumor promoter, has been shown to correlate with increased development of colorectal adenomas and progression to carcinoma. Herein we investigate the mechanism by which DCA leads to EGFR-MAPK activation, a candidate mechanism by which DCA may promote colorectal tumorigenesis. DCA treated colon cancer cells exhibited strong and prolonged activation of ERK1/2 when compared to EGF treatment alone. We also showed that DCA treatment prevents EGFR degradation as opposed to the canonical EGFR recycling observed with EGF treatment. Moreover, the combination of DCA and EGF treatment displayed synergistic activity, suggesting DCA activates MAPK signaling in a non-canonical manner. Further evaluation showed that DCA treatment increased intracellular calcium levels and CAMKII phosphorylation, and that blocking calcium with BAPTA-AM abrogated MAPK activation induced by DCA, but not by EGF. Finally we showed that DCA-induced CAMKII leads to MAPK activation through the recruitment of c-Src. Taken together, we demonstrated that DCA regulates MAPK activation through calcium signaling, an alternative mechanism not previously recognized in human colon cancer cells. Importantly, this mechanism allows for EGFR to escape degradation and thus achieve a constitutively active state, which may explain its tumor promoting effects.
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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.