ArticleBMC cancer2014
MTDH mediates trastuzumab resistance in HER2 positive breast cancer by decreasing PTEN expression through an NFκB-dependent pathway.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Association of MTDH immunohistochemical expression with metastasis and prognosis in female reproduction malignancies: a systematic review and meta-analysis.Scientific reports · 2016Pooled it
- Protein modification systems as cancer biomarkers and therapeutic targets.Precision clinical medicine · 2026Review
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- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- LncRNA DDX11-AS1 promotes breast cancer progression by targeting the miR-30c-5p/MTDH axis.Scientific reports · 2024Article
- Metadherin Regulates Inflammatory Breast Cancer Invasion and Metastasis.International journal of molecular sciences · 2023Article
- Mammaglobin 1 mediates progression of trastuzumab-resistant breast cancer cells through regulation of cyclins and NF-κB.FEBS open bio · 2022Article
- METTL1 promotes neuroblastoma development through mBiomarker research · 2022Article
- Disulfiram/copper induces antitumor activity against gastric cancer cells in vitro and in vivo by inhibiting S6K1 and c-Myc.Cancer chemotherapy and pharmacology · 2022Article
- Review
- MiR-128 suppresses metastatic capacity by targeting metadherin in breast cancer cells.Biological research · 2020Article
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- Activation of EMT in colorectal cancer by MTDH/NF-κB p65 pathway.Molecular and cellular biochemistry · 2019Article
- Metadherin: A Therapeutic Target in Multiple Cancers.Frontiers in oncology · 2019Review
- Efficient and tumor-specific knockdown of MTDH gene attenuates paclitaxel resistance of breast cancer cells both in vivo and in vitro.Breast cancer research : BCR · 2018Article
- Notch-1-PTEN-ERK1/2 signaling axis promotes HER2+ breast cancer cell proliferation and stem cell survival.Oncogene · 2018Article
- MicroRNA-584 inhibits cell proliferation and invasion in non-small cell lung cancer by directly targeting MTDH.Experimental and therapeutic medicine · 2018Article
- microRNA-1471 suppresses glioma cell growth and invasion by repressing metadherin expression.International journal of clinical and experimental pathology · 2018Article
- NF-κB p65 Overexpression Promotes Bladder Cancer Cell Migration via FBW7-Mediated Degradation of RhoGDIα Protein.Neoplasia (New York, N.Y.) · 2017Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTrastuzumab resistance is almost inevitable in the management of human epidermal growth factor receptor (HER) 2 positive breast cancer, in which phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss is implicated. Since metadherin (MTDH) promotes malignant phenotype of breast cancer, we sought to define whether MTDH promotes trastuzumab resistance by decreasing PTEN expression through an NFκB-dependent pathway.
methodsThe correlations between MTDH and PTEN expressions were analyzed both in HER2 positive breast cancer tissues and trastuzumab resistant SK-BR-3 (SK-BR-3/R) cells. Gene manipulations of MTDH and PTEN levels by knockdown or overexpression were utilized to elucidate molecular mechanisms of MTDH and PTEN implication in trastuzumab resistance. For in vivo studies, SK-BR-3 and SK-BR-3/R cells and modified derivatives were inoculated into nude mice alone or under trastuzumab exposure. Tumor volumes, histological examinations as well as Ki67 and PTEN expressions were revealed.
resultsElevated MTDH expression indicated poor clinical benefit, shortened progression free survival time, and was negatively correlated with PTEN level both in HER2 positive breast cancer patients and SK-BR-3/R cells. MTDH knockdown restored PTEN expression and trastuzumab sensitivity in SK-BR-3/R cells, while MTDH overexpression prevented SK-BR-3 cell death under trastuzumab exposure, probably through IκBα inhibition and nuclear translocation of p65 which subsequently decreased PTEN expression. Synergized effect of PTEN regulation were observed upon MTDH and p65 co-transfection. Forced PTEN expression in SK-BR-3/R cells restored trastuzumab sensitivity. Furthermore, decreased tumor volume and Ki67 level as well as increased PTEN expression were observed after MTDH knockdown in subcutaneous breast cancer xenografts from SK-BR-3/R cells, while the opposite effect were found in grafts from MTDH overexpressing SK-BR-3 cells.
conclusionsMTDH overexpression confers trastuzumab resistance in HER2 positive breast cancer. MTDH mediates trastuzumab resistance, at least in part, by PTEN inhibition through an NFκB-dependent pathway, which may be utilized as a promising therapeutic target for HER2 positive breast cancer.
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