ReferenceID 136
HER2 mediated de novo production of TGFβ leads to SNAIL driven epithelial-to-mesenchymal transition and metastasis of breast cancer
Mol Oncol
HER2 is an important determinant of poor prognosis in breast cancer patients. Studies indicate that HER2 positive tumors are mostly resistant to therapy and have high metastatic potential however, the underlying mechanis
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Record Fields
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- Reference Id
- 136
- Evidence Id
- 16726
- Core Evidence Id
- 16726
- Source Reference Id
- 235
- Herb2 Reference Id
- HBREF000443
- Subject Paper Key
- HBIN021845_24994678
- Pubmed Id
- 24994678
- Doi
- 10.1016/j.molonc.2014.06.006
- Paper Title
- HER2 mediated de novo production of TGFβ leads to SNAIL driven epithelial-to-mesenchymal transition and metastasis of breast cancer
- Paper Abstract
- HER2 is an important determinant of poor prognosis in breast cancer patients. Studies indicate that HER2 positive tumors are mostly resistant to therapy and have high metastatic potential however, the underlying mechanisms remain unknown. In this study, MDA-MB-231 and MCF-7 breast cancer cells with their HER2 overexpressing syngeneic variants were used to delineate the role of HER2 in EMT and metastasis. Our results demonstrated that HER2 overexpression increased the invasive potential of cells. Our results also showed that HER2 overexpression lead to the production of TGFβ resulting in the activation of TGFβ/SMAD signaling. Furthermore, activation of SNAIL, SLUG and ZEB-1, the transcriptional repressors of E-cadherin and increased mesenchymal characteristics were observed in high HER2 cells. Interestingly, EMT by HER2 was mediated through TGFβ. Intravenous injection of high HER2 MDA-MB-231 (HH) cells in athymic nude mice showed early and substantial metastasis as compared to the parent cells establishing the direct role of HER2 in metastasis. Our results showed that inhibition of HER2 mediated EMT by cucurbitacin B a triterpenoid, resulted in the suppression of brain metastasis of breast cancer cells. Taken together, our results identify a novel mechanism of HER2 in promoting breast cancer metastasis through de novo synthesis of TGFβ leading to EMT, an initial and essential step of metastasis.
- Journal
- Mol Oncol
- Publish Year
- 2014
- Experiment Subject
- mda-mb-231 and mcf-7 breast cancer cells ,nude mice
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- HER2 mediated de novo production of TGFβ leads to SNAIL driven epithelial-to-mesenchymal transition and metastasis of breast cancer
- Bilingual Status
- semi_complete