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Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
Pharmacological Inhibition of Necroptosis Promotes Human Breast Cancer Cell Proliferation and Metastasis
Feng Shen1, Xiangou Pan2, Min Li3
1Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, People's Republic of China.
Background:
Breast cancer remains a great threat to females worldwide. As a recently defined programmed cell death pathway that associates with immune activation, RIP1/RIP3/MLKL necroptosis signaling has been implicated in a variety of diseases. The present study aimed to investigate the role of RIP1/RIP3/MLKL signaling in breast cancer cell proliferation and metastasis in vivo and in vitro.
Methods:
Western blot and quantitative real-time PCR were performed to evaluate the activation of necroptosis signaling in clinical human breast cancer tissues. Correlation of necroptosis signaling markers with clinicopathological parameters was statistically assessed. Cell viability assay, colony formation assay, wound healing assay, and transwell migration and invasion assays were performed to investigate the effects of necroptosis inhibition on breast cancer cell proliferation and metastasis.
Results:
Clinical breast cancer tissues showed significantly higher levels of tumor necrosis factor alpha (TNFα), RIP1, RIP3 and MLKL at both mRNA and protein levels as compared with their paired non-cancerous tissues. Phosphorylation of RIP3 and MLKL was also remarkably provoked. Statistics showed that both RIP1 and MLKL positively correlated with cancer parameters such as N-cadherin (p=0.002 for RIP1 and p=0.021 for MLKL) and Ki67 (p=0.031 for RIP1 and p=0.05 for MLKL). The MLKL expression level significantly correlated with tumor size (p=0.001) and the proliferation indicator Ki67 (p=0.018). In addition, pharmacological inhibition of the necroptosis signaling using necrostatin-1 promoted breast cancer cell proliferation and colony formation by approximately 50%. Blockade of necroptosis signaling also accelerated wound healing process and cell transmigration in breast cancer cells.
Conclusion:
Our results suggested that pharmacological inhibition of necroptosis promoted breast cancer cell proliferation and metastasis. Modulation of tumor cell necroptosis might represent a novel strategy as to breast cancer treatment.
Insights
Inhibiting necroptosis signaling, a programmed cell death pathway, unexpectedly accelerated breast cancer cell proliferation and metastasis. Targeting tumor cell necroptosis may offer a new therapeutic strategy for breast cancer treatment.
Area of Science:
- Oncology
- Cell Death Mechanisms
- Molecular Biology
Background:
- Breast cancer poses a significant global health threat to women.
- Necroptosis, a programmed cell death pathway linked to immune activation, is implicated in various diseases.
- The role of RIP1/RIP3/MLKL necroptosis signaling in breast cancer progression requires investigation.
Purpose of the Study:
- To investigate the role of RIP1/RIP3/MLKL necroptosis signaling in breast cancer cell proliferation and metastasis.
- To evaluate the impact of necroptosis inhibition on breast cancer progression in vitro and in vivo.
Main Methods:
- Western blot and qRT-PCR to assess necroptosis signaling markers in clinical breast cancer tissues.
- Statistical analysis of necroptosis markers against clinicopathological parameters.
- In vitro assays (viability, colony formation, migration, invasion) to determine effects of necroptosis inhibition.
Main Results:
- Elevated RIP1, RIP3, MLKL, and TNFα levels in breast cancer tissues compared to normal tissues.
- Increased phosphorylation of RIP3 and MLKL observed in tumors.
- Necrostatin-1 inhibition of necroptosis promoted breast cancer cell proliferation, colony formation, wound healing, and migration.
Conclusions:
- Pharmacological inhibition of necroptosis enhances breast cancer cell proliferation and metastasis.
- Targeting tumor cell necroptosis presents a potential novel therapeutic strategy for breast cancer.
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