ArticleJournal of experimental & clinical cancer research : CR2018
GDF15 promotes the proliferation of cervical cancer cells by phosphorylating AKT1 and Erk1/2 through the receptor ErbB2.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed, 209 citations in OpenAlex.
- Association Between Circulating GDF-15 and Cardio-Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS Trial.Journal of the American Heart Association · 2021Trial
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Lactylation of GDF15 Regulates Angiogenesis in Ischemic Stroke via Activating PI3K/AKT/mTOR Pathway.Molecular neurobiology · 2026Article
- GDF15 in Liver Fibrosis: Molecular Mechanisms, Immunoregulatory Functions, and Therapeutic Potential.Biomolecules · 2026Review
- Oncogene c‑Myc: From molecular mechanism to targeted therapy (Review).Molecular medicine reports · 2026Review
- Gdf15 expression in thermogenic adipocytes regulates diet-induced weight gain in a sex-dependent manner.Molecular medicine (Cambridge, Mass.) · 2026Article
- Context-Dependent Role of GDF15: GDF15Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nucleoporin TPR integrates MAPK signaling with mitogen-induced transcriptional programs.Cell death & disease · 2026Article
- GFRAL is required to mediate changes in systemic metabolism in response to mitochondrial stress in brown adipose tissue.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Molecular characteristics of proximal and distal esophagogastric junction adenocarcinoma.Journal of thoracic disease · 2026Article
- SENP3 drives colorectal cancer progression by enhancing GDF15 expression.International journal of colorectal disease · 2026Article
- Assessment of the anticancer and antimetastatic effects of monocarbonyl analogs of curcumin, C66 and B2BrBC, in breast cancer cells.Cancer cell international · 2026Article
- Mycosubtilin Induces G1 Phase Block and Autophagy in Cervical Cancer HeLa Cells.Probiotics and antimicrobial proteins · 2026Article
- GDF15 as a sentinel of metabolic integrity: a narrative review of stress signaling, multisystem pathophysiology, and therapeutic potential.Frontiers in endocrinology · 2026Review
- GDF15 predisposes aortic dissection through regulation of vascular smooth muscle cell proliferation and phenotypic change via the ERK/Akt pathway.American journal of translational research · 2026Article
- The identification of metabolites from gut microbiota in HPV infection via network pharmacology.PloS one · 2026Article
- MYO1B in human disease: an actin-based motor linking membrane trafficking to oncogenic signaling, metastasis, and vascular aging.Frontiers in oncology · 2026Review
- Recent advancement in inflammatory biomarkers for cervical cancer diagnosis and therapy.Frontiers in oncology · 2026Review
- TMEM121 suppresses cervical cancer cell proliferation and migration via interaction with the ERK pathway.American journal of cancer research · 2026Article
- Growth/Differentiation Factor 15 Promotes a Pro-Regenerative Response in Chondrocytes Upon Cartilage Injury.MedComm · 2025Article
75 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGrowth differentiation factor 15 (GDF15) is a member of the TGF-β superfamily, and evidence suggests that a substantial amount of GDF15 is secreted in various human cancers, such as ovarian cancer, prostate cancer, and breast cancer, among others. However, the function of GDF15 in cervical cancer has not yet been reported.
methodsImmunohistochemistry was used to detect GDF15 expression in normal cervix and in different cervical cancer lesions. Cell growth curves, MTT, tumor formation assays and flow cytometry were utilized to observe the effects of ectopic GDF15 expression on the proliferation and cell cycle of cervical cancer cells. Real-time PCR, western blotting and immunoprecipitation assays were conducted to measure the expression of genes related to the cell cycle and the PI3K/AKT and MAPK/ERK signaling pathways. A chromatin immunoprecipitation assay was performed to confirm whether C-myc bound to a specific region of the GDF15 promoter. Inhibitor treatment and immunoprecipitation assays were employed to identify the association between GDF15 and ErbB2.
resultsGDF15 expression gradually increased during the progression of cervical carcinogenesis. GDF15 promoted cervical cancer cell proliferation via exogenous rhGDF15 treatment or the use of gene editing technology in vitro and in vivo and significantly accelerated the cell cycle transition from G0/G1 to S phase. The expression of p-ErbB2, p-AKT1, p-Erk1/2, CyclinD1 and CyclinE1 was up-regulated and the expression of p21 was down-regulated in GDF15-overexpressing and rhGDF15-treated cervical cancer cells. C-myc trans-activated GDF15 expression by binding to the E-box motifs in the promoter of GDF15 and contributed to the positive feedback of GDF15/C-myc/GDF15. Furthermore, GDF15 bound to ErbB2 in a protein complex in cervical cancer cells.
conclusionsOur data demonstrated that GDF15 promoted the proliferation of cervical cancer cells via the up-regulation of CyclinD1 and CyclinE1 and the down-regulation of p21 through both the PI3K/AKT and MAPK/ERK signaling pathways in a complex with ErbB2.
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