Leptin Signaling in Breast Cancer Pathophysiology
Summary
Leptin, a hormone predominantly secreted by adipose tissue, exerts pleiotropic effects on cellular metabolism, proliferation and inflammatory pathways. In the context of breast cancer, elevated leptin levels—frequently observed in individuals with obesity—contribute to tumour initiation, progression and resistance to therapy. Leptin binds to its cognate receptor (Ob-R) on mammary epithelial and stromal cells, activating downstream cascades including JAK/STAT, PI3K/AKT and MAPK/ERK. These pathways drive cell cycle progression, angiogenesis and suppression of apoptosis. Crosstalk between leptin and oestrogen signalling amplifies mitogenic stimuli in hormone-sensitive tumours, while interactions with other adipokines and cytokines shape a pro-tumourigenic microenvironment. Moreover, leptin modulates epithelial polarity and supports epithelial-to-mesenchymal transition, facilitating invasion and metastasis. Together, these mechanisms underpin the mechanistic link between obesity, hyperleptinaemia and poor breast cancer outcomes, highlighting leptin signalling as a compelling target for risk reduction and therapeutic intervention.
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Leptin Signaling in Breast Cancer Pathophysiology publication trend
The graph below shows the total number of articles in leptin signaling in breast cancer pathophysiology across all publications each year (not limited to Nature Index journals).
Technical terms
Leptin: An adipocyte-derived hormone that regulates energy balance and modulates cell proliferation, angiogenesis and immune responses.
Adipokine: A bioactive peptide secreted by adipose tissue that influences metabolic, inflammatory and proliferative pathways.
Epithelial polarity: The organised spatial arrangement of cellular structures within epithelial cells that maintains tissue architecture and barrier function.
Hyperleptinaemia: Elevated circulating levels of leptin, often associated with increased adiposity and altered cell signalling.
JAK/STAT pathway: A key intracellular signalling cascade, activated by cytokines and hormones, that controls gene expression linked to proliferation and survival.
References
- Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link. Journal of the National Cancer Center (2024).
- Reversion of breast epithelial polarity alterations caused by obesity. npj Breast Cancer (2023).
- Obesity, Leptin and Breast Cancer: Epidemiological Evidence and Proposed Mechanisms. Cancers (2019).
- Leptin produced by obese adipose stromal/stem cells enhances proliferation and metastasis of estrogen receptor positive breast cancers. Breast Cancer Research (2015).
- Leptin-induced Epithelial-Mesenchymal Transition in Breast Cancer Cells Requires β-Catenin Activation via Akt/GSK3- and MTA1/Wnt1 Protein-dependent Pathways*. Journal of Biological Chemistry (2012).
- The Multifaceted Mechanism of Leptin Signaling within Tumor Microenvironment in Driving Breast Cancer Growth and Progression. Frontiers in Oncology (2014).
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