ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc
Abstract Background Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat, because it is so aggressive with shorter survival. Chemotherapy remains the standard treatment due to the lack of specific and effective molecular targets. The aim of the present study is...
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-020-01727-5 |
| _version_ | 1818728481693892608 |
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| author | Yuanyuan Cheng Lishuang Lin Xiaoyan Li Aiqi Lu Chenjian Hou Qian Wu Xiaomu Hu Zhongwen Zhou Zhongqing Chen Feng Tang |
| author_facet | Yuanyuan Cheng Lishuang Lin Xiaoyan Li Aiqi Lu Chenjian Hou Qian Wu Xiaomu Hu Zhongwen Zhou Zhongqing Chen Feng Tang |
| author_sort | Yuanyuan Cheng |
| collection | DOAJ |
| description | Abstract Background Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat, because it is so aggressive with shorter survival. Chemotherapy remains the standard treatment due to the lack of specific and effective molecular targets. The aim of the present study is to investigate the potential roles of A Disintegrin and Metalloproteinase 10 (ADAM10) on TNBC cells and the effects of combining ADAM10 expression and neoadjuvant chemotherapy treatment (NACT) to improve the overall survival in breast cancer patients. Methods Using a series of breast cancer cell lines, we measured the expression of ADAM10 and its substrates by quantitative real-time PCR assay (qRT-PCR) and western blot analysis. Cell migration and invasion, cell proliferation, drug sensitivity assay, cell cycle and apoptosis were conducted in MDA-MB-231 cells cultured with ADAM10 siRNA. The effect of ADAM10 down-regulation by siRNA on its substrates was assessed by western blot analysis. We performed immunohistochemical staining for ADAM10 in clinical breast cancer tissues in 94 patients receiving NACT. Results The active form of ADAM10 was highly expressed in TNBC cell lines. Knockdown of ADAM10 in MDA-MB-231 cells led to a significant decrease in cell proliferation, migration, invasion and the IC50 value of paclitaxel and adriamycin, while induced cell cycle arrest and apoptosis. And these changes were correlated with down-regulation of Notch signaling, CD44 and cellular prion protein (PrPc). In clinical breast cancer cases, a high ADAM10 expression in pre-NACT samples was strongly associated with poorer response to NACT and shorter overall survival. Conclusions These data suggest the previously unrecognized roles of ADAM10 in contributing to the progression and chemo-resistance of TNBC. |
| first_indexed | 2024-12-17T22:30:41Z |
| format | Article |
| id | doaj.art-6e1e700382d54aaabda92f39b392f827 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-17T22:30:41Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-6e1e700382d54aaabda92f39b392f8272022-12-21T21:30:13ZengBMCCancer Cell International1475-28672021-01-0121111510.1186/s12935-020-01727-5ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPcYuanyuan Cheng0Lishuang Lin1Xiaoyan Li2Aiqi Lu3Chenjian Hou4Qian Wu5Xiaomu Hu6Zhongwen Zhou7Zhongqing Chen8Feng Tang9Department of Pathology, Huashan Hospital, Fudan UniversityDepartment of Pathology, Huashan Hospital, Fudan UniversityDepartment of Surgery, Huashan Hospital, Fudan UniversityDepartment of Pathology, Huashan Hospital, Fudan UniversityDepartment of Pathology, School of Basic Medical Sciences, Fudan UniversityDepartment of Pathology, Huashan Hospital, Fudan UniversityDepartment of Pathology, Huashan Hospital, Fudan UniversityDepartment of Pathology, Huashan Hospital, Fudan UniversityDepartment of Pathology, Huashan Hospital, Fudan UniversityDepartment of Pathology, Huashan Hospital, Fudan UniversityAbstract Background Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat, because it is so aggressive with shorter survival. Chemotherapy remains the standard treatment due to the lack of specific and effective molecular targets. The aim of the present study is to investigate the potential roles of A Disintegrin and Metalloproteinase 10 (ADAM10) on TNBC cells and the effects of combining ADAM10 expression and neoadjuvant chemotherapy treatment (NACT) to improve the overall survival in breast cancer patients. Methods Using a series of breast cancer cell lines, we measured the expression of ADAM10 and its substrates by quantitative real-time PCR assay (qRT-PCR) and western blot analysis. Cell migration and invasion, cell proliferation, drug sensitivity assay, cell cycle and apoptosis were conducted in MDA-MB-231 cells cultured with ADAM10 siRNA. The effect of ADAM10 down-regulation by siRNA on its substrates was assessed by western blot analysis. We performed immunohistochemical staining for ADAM10 in clinical breast cancer tissues in 94 patients receiving NACT. Results The active form of ADAM10 was highly expressed in TNBC cell lines. Knockdown of ADAM10 in MDA-MB-231 cells led to a significant decrease in cell proliferation, migration, invasion and the IC50 value of paclitaxel and adriamycin, while induced cell cycle arrest and apoptosis. And these changes were correlated with down-regulation of Notch signaling, CD44 and cellular prion protein (PrPc). In clinical breast cancer cases, a high ADAM10 expression in pre-NACT samples was strongly associated with poorer response to NACT and shorter overall survival. Conclusions These data suggest the previously unrecognized roles of ADAM10 in contributing to the progression and chemo-resistance of TNBC.https://doi.org/10.1186/s12935-020-01727-5A disintegrin and metalloproteinase 10 (ADAM10)Triple-negative breast cancer (TNBC)Notch1 signalingCD44Cellular prion protein (PrPc) |
| spellingShingle | Yuanyuan Cheng Lishuang Lin Xiaoyan Li Aiqi Lu Chenjian Hou Qian Wu Xiaomu Hu Zhongwen Zhou Zhongqing Chen Feng Tang ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc Cancer Cell International A disintegrin and metalloproteinase 10 (ADAM10) Triple-negative breast cancer (TNBC) Notch1 signaling CD44 Cellular prion protein (PrPc) |
| title | ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc |
| title_full | ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc |
| title_fullStr | ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc |
| title_full_unstemmed | ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc |
| title_short | ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc |
| title_sort | adam10 is involved in the oncogenic process and chemo resistance of triple negative breast cancer via regulating notch1 signaling pathway cd44 and prpc |
| topic | A disintegrin and metalloproteinase 10 (ADAM10) Triple-negative breast cancer (TNBC) Notch1 signaling CD44 Cellular prion protein (PrPc) |
| url | https://doi.org/10.1186/s12935-020-01727-5 |
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