Exercise-Induced Catecholamines Activate the Hippo Tumor Suppressor Pathway to Reduce Risks of Breast Cancer...

Area of Science:

• Oncology
• Exercise Physiology
• Molecular Biology

Background:

• Epidemiologic studies show physical activity reduces breast cancer risk, recurrence, and mortality.
• The precise biological mechanisms underlying exercise's protective effects remain largely unidentified.

Purpose of the Study:

• To identify exercise-induced factors and signaling pathways that suppress breast cancer growth.
• To elucidate the mechanisms behind exercise-mediated breast cancer suppression.

Main Methods:

• Incubation of breast cancer cells (MCF-7 and MDA-MB-231) with human exercise-conditioned serum.
• In vivo studies using murine models with exercise interventions (running wheels).
• Analysis of cell viability, tumor growth, and the Hippo signaling pathway, including YAP phosphorylation and downstream gene expression.

Main Results:

• Exercise-conditioned serum significantly decreased breast cancer cell viability and reduced tumor formation in mice.
• Blockade of β-adrenergic signaling abolished the exercise-serum effect, identifying catecholamines (epinephrine and norepinephrine) as key factors.
• Epinephrine and norepinephrine directly inhibited cancer cell viability and tumor growth by activating the Hippo signaling pathway, leading to YAP retention and reduced target gene expression.
• Murine models with running wheels exhibited reduced tumor growth and enhanced Hippo pathway regulation.

Conclusions:

• Catecholamines mediate the breast cancer-suppressive effects of physical activity.
• The Hippo signaling pathway is a key mediator of exercise's anti-cancer effects.
• Findings provide a mechanistic basis for the observed benefits of physical activity in breast cancer prevention and treatment.