Ang II-AT1R increases cell migration through PI3K/AKT and NF-κB pathways in breast cancer

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Angiotensin II (Ang II), a key peptide in the renin-angiotensin system (RAS), is implicated in promoting cell migration.
• The Angiotensin II type 1 receptor (AT1R) mediates Ang II's biological effects, including those in cancer progression.

Purpose of the Study:

• To elucidate the molecular mechanisms by which Ang II enhances cell migration in AT1R-positive MDA-MB-231 human breast cancer cells.
• To investigate the role of the AT1R/PI3K/Akt/NF-κB signaling pathway in Ang II-induced breast cancer cell migration and matrix metalloproteinase (MMP) expression.

Main Methods:

• Utilized MDA-MB-231 human breast cancer cells.
• Assessed the effects of Ang II on cell migration and MMP-2/MMP-9 expression.
• Employed specific inhibitors for AT1R, PI3K, Akt, NF-κB, MMP-2, and MMP-9.
• Analyzed the phosphorylation status of PI3K and Akt, and NF-κB activity.

Main Results:

• Ang II dose-dependently increased breast cancer cell migration and MMP-2/MMP-9 expression.
• Inhibition of MMP-2, MMP-9, AT1R, PI3K, Akt, or NF-κB attenuated Ang II-mediated cell migration.
• Ang II induced PI3K and Akt phosphorylation, leading to increased NF-κB activity.
• AT1R and PI3K inhibition downregulated Ang II-mediated MMP-2/MMP-9 expression.

Conclusions:

• Ang II activates the AT1R/PI3K/Akt pathway, subsequently activating IKKα/β and NF-κB.
• This signaling cascade results in enhanced MMP-2/MMP-9 expression and increased migration in human breast cancer cells.
• Targeting the Ang II/AT1R/PI3K/Akt/NF-κB pathway presents a potential anti-metastatic therapeutic strategy for breast cancer.