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Park, Jiyoung
Molecular Metabolism Laboratory (MML)
Research Interests
  • Obesity, diabetes, adipose tissue, cancer, cancer-associated adipocyte, dermal adipocyte, metabolic memory

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Leptin Receptor Signaling Supports Cancer Cell Metabolism through Suppression of Mitochondrial Respiration in Vivo

Cited 22 times inthomson ciCited 22 times inthomson ci
Title
Leptin Receptor Signaling Supports Cancer Cell Metabolism through Suppression of Mitochondrial Respiration in Vivo
Author
Park, JiyoungKusminski, Christine M.Chua, Streamson C.Scherer, Philipp E.
Keywords
BREAST-CANCER;  MAMMARY-TUMORS;  TRANSGENIC COMPLEMENTATION;  GROWTH-FACTOR;  FEMALE MICE;  DB/DB MICE;  STAT3;  EXPRESSION;  ONCOGENE;  OBESITY
Issue Date
2010-12
Publisher
AMER SOC INVESTIGATIVE PATHOLOGY, INC
Citation
AMERICAN JOURNAL OF PATHOLOGY, v.177, no.6, pp.3133 - 3144
Abstract
Obesity represents a risk factor for certain types of cancer. Leptin, a hormone predominantly produced by adipocytes, is elevated in the obese state. In the context of breast cancer, leptin derived from local adipocytes is present at high concentrations within the mammary gland. A direct physiological role of peripheral leptin action in the tumor microenvironment in vivo has not yet been examined. Here, we report that mice deficient in the peripheral leptin receptor, while harboring an intact central leptin signaling pathway, develop a fully mature ductal epithelium, a phenomenon not observed in db/db mice to date. In the context of the MMTV-PyMT mammary tumor model, the lack of peripheral leptin receptors attenuated tumor progression and metastasis through a reduction of the ERK1/2 and Jak2/STAT3 pathways. These are tumor cell-autonomous properties, independent of the metabolic state of the host. In the absence of leptin receptor signaling, the metabolic phenotype is less reliant on aerobic glycolysis and displays an enhanced capacity for β-oxidation, in contrast to nontransformed cells. Leptin receptor-free tumor cells display reduced STAT3 tyrosine phosphorylation on residue Y705 but have increased serine phosphorylation on residue S727, consistent with preserved mitochondrial function in the absence of the leptin receptor. Therefore, local leptin action within the mammary gland is a critical mediator, linking obesity and dysfunctional adipose tissue with aggressive tumor growth.
URI
https://scholarworks.unist.ac.kr/handle/201301/7167
DOI
10.2353/ajpath.2010.100595
ISSN
0002-9440
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