ArticlePloS one2016
Downregulation of AKT3 Increases Migration and Metastasis in Triple Negative Breast Cancer Cells by Upregulating S100A4.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
52 citing papers in PubMed, 99 citations in OpenAlex.
- Endometrial cancer: from clinical reality to molecular treatment.Discover oncology · 2025Review
- Targeting the AKT/mTOR pathway attenuates the metastatic potential of colorectal carcinoma circulating tumor cells in a murine xenotransplantation model.Molecular oncology · 2025Article
- Signaling pathway dysregulation in breast cancer.Oncotarget · 2025Review
- AXL-TBK1 driven AKT3 activation promotes metastasis.Science signaling · 2024Article
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- TNA-Mediated Antisense Strategy to Knockdown Akt Genes for Triple-Negative Breast Cancer Therapy.Small methods · 2024Article
- Ikaros sets the threshold for negative B-cell selection by regulation of the signaling strength of the AKT pathway.Cell communication and signaling : CCS · 2024Article
- All Three AKT Isoforms Can Upregulate Oxygen Metabolism and Lactate Production in Human Hepatocellular Carcinoma Cell Lines.International journal of molecular sciences · 2024Article
- K-Ras(V12) differentially affects the three Akt isoforms in lung and pancreatic carcinoma cells and upregulates E-cadherin and NCAM via Akt3.Cell communication and signaling : CCS · 2024Article
- Major regulators of the multi-step metastatic process are potential therapeutic targets for breast cancer management.Functional & integrative genomics · 2023Article
- Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors HarboringCancer research communications · 2023Article
- Dialog beyond the Grave: Necrosis in the Tumor Microenvironment and Its Contribution to Tumor Growth.International journal of molecular sciences · 2023Review
- Changes of Mutations and Copy-Number and Enhanced Cell Migration during Breast Tumorigenesis.Advanced biology · 2023Article
- Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma.World journal of clinical oncology · 2023Article
- A comprehensive transcriptomic analysis of the bisphenol A affected kidney in mice.Frontiers in molecular biosciences · 2023Article
- Identification and development of a subtype-selective allosteric AKT inhibitor suitable for clinical development.Scientific reports · 2022Article
- hnRNP A1 and hnRNP C associate with miR-17 and miR-18 in thyroid cancer cells.FEBS open bio · 2022Article
- Article
- Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target.Nature communications · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTreatment of breast cancer patients with distant metastases represents one of the biggest challenges in today's gynecological oncology. Therefore, a better understanding of mechanisms promoting the development of metastases is of paramount importance. The serine/threonine kinase AKT was shown to drive cancer progression and metastasis. However, there is emerging data that single AKT isoforms (i.e. AKT1, AKT2 and AKT3) have different or even opposing functions in the regulation of cancer cell migration in vitro, giving rise to the hypothesis that inhibition of distinct AKT isoforms might have undesirable effects on cancer dissemination in vivo.
methodsThe triple negative breast cancer cell line MDA-MB-231 was used to investigate the functional roles of AKT in migration and metastasis. AKT single and double knockdown cells were generated using isoform specific shRNAs. Migration was analyzed using live cell imaging, chemotaxis and transwell assays. The metastatic potential of AKT isoform knockdown cells was evaluated in a subcutaneous xenograft mouse model in vivo.
resultsDepletion of AKT3, but not AKT1 or AKT2, resulted in increased migration in vitro. This effect was even more prominent in AKT2,3 double knockdown cells. Furthermore, combined downregulation of AKT2 and AKT3, as well as AKT1 and AKT3 significantly increased metastasis formation in vivo. Screening for promigratory proteins revealed that downregulation of AKT3 increases the expression of S100A4 protein. In accordance, depletion of S100A4 by siRNA approach reverses the increased migration induced by knockdown of AKT3.
conclusionsWe demonstrated that knockdown of AKT3 can increase the metastatic potential of triple negative breast cancer cells. Therefore, our results provide a rationale for the development of AKT isoform specific inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
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.