ArticleOncotarget2016
Anti-cancer drug 3,3'-diindolylmethane activates Wnt4 signaling to enhance gastric cancer cell stemness and tumorigenesis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- 3,3'-Diindolylmethane blocks the dissemination of gastric cancer cells in the peritoneal cavity through the MFGE8-MAPK/ERK signaling pathway.Cancer cell international · 2025Article
- Identification of a key smooth muscle cell subset driving ischemic cardiomyopathy progression through single-cell RNA sequencing.Scientific reports · 2025Article
- Emerging roles and biomarker potential of WNT6 in human cancers.Cell communication and signaling : CCS · 2024Review
- Wnt signaling in gastric cancer: current progress and future prospects.Frontiers in oncology · 2024Review
- Gastric cancer and mesenchymal stem cell-derived exosomes: from pro-tumorigenic effects to anti-cancer vehicles.Archives of pharmacal research · 2024Review
- miR-199a and miR-199b facilitate diffuse gastric cancer progression by targeting Frizzled-6.Scientific reports · 2023Article
- Anticancer applications of phytochemicals in gastric cancer: Effects and molecular mechanism.Frontiers in pharmacology · 2022Review
- Roles and action mechanisms of WNT4 in cell differentiation and human diseases: a review.Cell death discovery · 2021Review
- Regulation of carcinogenesis and mediation through Wnt/β-catenin signaling by 3,3'-diindolylmethane in an enzalutamide-resistant prostate cancer cell line.Scientific reports · 2021Article
- 3,3'-Diindolylmethane Promotes Gastric Cancer ProgressionFrontiers in oncology · 2021Article
- WNT4 secreted by tumor tissues promotes tumor progression in colorectal cancer by activation of the Wnt/β-catenin signalling pathway.Journal of experimental & clinical cancer research : CR · 2020Article
- PRMT5/Wnt4 axis promotes lymph-node metastasis and proliferation of laryngeal carcinoma.Cell death & disease · 2020Article
- The Emerging Role of GC-MSCs in the Gastric Cancer Microenvironment: From Tumor to Tumor Immunity.Stem cells international · 2019Review
- Exosomes Derived from Hypoxic Colorectal Cancer Cells Transfer Wnt4 to Normoxic Cells to Elicit a Prometastatic Phenotype.International journal of biological sciences · 2018Article
- Exosomes Derived From Hypoxic Colorectal Cancer Cells Promote Angiogenesis Through Wnt4-Induced β-Catenin Signaling in Endothelial Cells.Oncology research · 2017Article
- IL-17B activated mesenchymal stem cells enhance proliferation and migration of gastric cancer cells.Oncotarget · 2017Article
- Fentanyl Promotes Breast Cancer Cell Stemness and Epithelial-Mesenchymal Transition by Upregulating α1, 6-Fucosylation via Wnt/β-Catenin Signaling Pathway.Frontiers in physiology · 2017Article
- 3,3'-Diindolylmethane stimulates exosomal Wnt11 autocrine signaling in human umbilical cord mesenchymal stem cells to enhance wound healing.Theranostics · 2017Article
- Cellular and Molecular Mechanisms of 3,3'-Diindolylmethane in Gastrointestinal Cancer.International journal of molecular sciences · 2016Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a natural health supplement, 3,3'-diindolylmethane (DIM) is proposed as a preventive and chemotherapeutic agent for cancer by inhibiting cell proliferation and inducing cell apoptosis. However, we found that in contrary to high level of DIM (30 μM), low level of DIM (1 μM and 10 μM) obviously promoted gastric cancer cell growth and migration. In addition, we found that low level of DIM increased the expression of stemness factors and enhanced the pluripotency of gastric cancer cells. Low level of DIM promoted gastric cancer progression by inducing the PORCN-dependent secretion of Wnt4 and the activation of β-catenin signaling. Wnt4 knockdown reversed the effects of low level of DIM on gastric cancer cells. The results of in vivo studies showed that gastric cancer cells treated with low level of DIM (1 μM) grew faster and expressed higher level of Wnt4 than control cells. Taken together, our findings indicate that low level of DIM activates autocrine Wnt4 signaling to enhance the progression of gastric cancer, which may suggest an adverse aspect of DIM in cancer therapy. Our findings will provide a new aspect for the safety of DIM in its clinical application.
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Registered trials
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