Prognostic role of cyclin D2/D3 in multiple human malignant neoplasms: A systematic review and meta‐analysis

et al. 2021

Cancer Cell Int

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.

Section: Discussionmentioning

confidence: 99%

ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc

et al. 2021

Cancer Cell Int

“…The expression level of Notch1 targets Cyclin D3, HES1 and c-Myc is reduced, while p21 Waf1/Cip1 is increased. Cyclin D3 regulates the cell cycle by controlling physiological progression from G1 to S phase [41], whereas the tumor suppressor p21 Waf1/Cip1 acts as an inhibitor of cell cycle progression [42]. HES1 and c-Myc have been implicated in cancer [43].…”

Section: Discussionmentioning

confidence: 99%

ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc

et al. 2021

Preprint

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.

“…Meanwhile, the expression level of Notch1 targets Cyclin D3, HES1 and c-Myc is reduced and p21 Waf1/Cip1 is increased. Cyclin D3 regulates the cell cycle by controlling physiological progression from G1 to S phase [41], whereas the tumor suppressor p21 Waf1/Cip1 acts as an inhibitor of cell cycle progression [42]. HES1 and c-Myc have been implicated in cancer [43].…”

Section: Discussionmentioning

confidence: 99%

Primary Research ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc

et al. 2020

Preprint

Background Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat, generally more aggressive and with shorter overall survival. Chemotherapy remains the standard treatment due to the absence of specific and effective molecular targets. The aim of the present study was to investigate the potential roles of A Disintegrin and Metalloproteinase 10 (ADAM10) in TNBC cells and the relationship between ADAM10 expression and neoadjuvant chemotherapy treatment (NACT) effect and 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 from 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 PrPc. In clinical breast cancer cases, high ADAM10 expression in pre-NACT samples was strongly associated with poor response to NACT and short overall survival. Conclusions These data suggest previously unrecognized roles for ADAM10 in TNBC, involving in the progression and chemo-resistance of TNBC.