Leptin signaling in breast cancer: An overview

Donatella Cirillo, Anna Maria Rachiglio, Raffaele La Montagna, Antonio Giordano, Nicola Normanno

Research output: Contribution to journalArticle

Abstract

The adipocyte-derived peptide leptin acts through binding to specific membrane receptors, of which six isoforms (obRa-f) have been identified up to now. Binding of leptin to its receptor induces activation of different signaling pathways, including the JAK/STAT, MAPK, IRS1, and SOCS3 signaling pathways. Since the circulating levels of leptin are elevated in obese individuals, and excess body weight has been shown to increase breast cancer risk in postmenopausal women, several studies addressed the role of leptin in breast cancer. Expression of leptin and its receptors has been demonstrated to occur in breast cancer cell lines and in human primary breast carcinoma. Leptin is able to induce the growth of breast cancer cells through activation of the Jak/STAT3, ERK1/2, and/or PI3K pathways, and can mediate angiogenesis by inducing the expression of vascular endothelial growth factor (VEGF). In addition, leptin induces transactivation of ErbB-2, and interacts in triple negative breast cancer cells with insulin like growth factor-1 (IGF-1) to transactivate the epidermal growth factor receptor (EGFR), thus promoting invasion and migration. Leptin can also affect the growth of estrogen receptor (ER)-positive breast cancer cells, by stimulating aromatase expression and thereby increasing estrogen levels through the aromatization of androgens, and by inducing MAPK-dependent activation of ER. Taken together, these findings suggest that the leptin system might play an important role in breast cancer pathogenesis and progression, and that it might represent a novel target for therapeutic intervention in breast cancer.

Original languageEnglish
Pages (from-to)956-964
Number of pages9
JournalJournal of Cellular Biochemistry
Volume105
Issue number4
DOIs
Publication statusPublished - Jan 11 2008

Fingerprint

Leptin
Breast Neoplasms
Cells
Chemical activation
Estrogen Receptors
Triple Negative Breast Neoplasms
Aromatization
Leptin Receptors
Aromatase
Somatomedins
Growth
Phosphatidylinositol 3-Kinases
Epidermal Growth Factor Receptor
Adipocytes
Vascular Endothelial Growth Factor A
Transcriptional Activation
Androgens
Protein Isoforms
Estrogens
Body Weight

Keywords

  • Breast cancer
  • Leptin
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Cirillo, D., Rachiglio, A. M., La Montagna, R., Giordano, A., & Normanno, N. (2008). Leptin signaling in breast cancer: An overview. Journal of Cellular Biochemistry, 105(4), 956-964. https://doi.org/10.1002/jcb.21911

Leptin signaling in breast cancer : An overview. / Cirillo, Donatella; Rachiglio, Anna Maria; La Montagna, Raffaele; Giordano, Antonio; Normanno, Nicola.

In: Journal of Cellular Biochemistry, Vol. 105, No. 4, 11.01.2008, p. 956-964.

Research output: Contribution to journalArticle

Cirillo, D, Rachiglio, AM, La Montagna, R, Giordano, A & Normanno, N 2008, 'Leptin signaling in breast cancer: An overview', Journal of Cellular Biochemistry, vol. 105, no. 4, pp. 956-964. https://doi.org/10.1002/jcb.21911
Cirillo D, Rachiglio AM, La Montagna R, Giordano A, Normanno N. Leptin signaling in breast cancer: An overview. Journal of Cellular Biochemistry. 2008 Jan 11;105(4):956-964. https://doi.org/10.1002/jcb.21911
Cirillo, Donatella ; Rachiglio, Anna Maria ; La Montagna, Raffaele ; Giordano, Antonio ; Normanno, Nicola. / Leptin signaling in breast cancer : An overview. In: Journal of Cellular Biochemistry. 2008 ; Vol. 105, No. 4. pp. 956-964.
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