Leptin signaling in breast cancer: an overview
- PMID:18821585
- DOI: 10.1002/jcb.21911
Leptin signaling in breast cancer: an overview
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.
Similar articles
- Evidence that leptin through STAT and CREB signaling enhances cyclin D1 expression and promotes human endometrial cancer proliferation.Catalano S, Giordano C, Rizza P, Gu G, Barone I, Bonofiglio D, Giordano F, Malivindi R, Gaccione D, Lanzino M, De Amicis F, Andò S.Catalano S, et al.J Cell Physiol. 2009 Mar;218(3):490-500. doi: 10.1002/jcp.21622.J Cell Physiol. 2009.PMID:18988190
- Adverse effects of obesity on breast cancer prognosis, and the biological actions of leptin (review).Rose DP, Gilhooly EM, Nixon DW.Rose DP, et al.Int J Oncol. 2002 Dec;21(6):1285-92.Int J Oncol. 2002.PMID:12429979Review.
- Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells.Cascio S, Ferla R, D'Andrea A, Gerbino A, Bazan V, Surmacz E, Russo A.Cascio S, et al.J Cell Physiol. 2009 Oct;221(1):189-94. doi: 10.1002/jcp.21843.J Cell Physiol. 2009.PMID:19492417
- Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression.Perera CN, Chin HG, Duru N, Camarillo IG.Perera CN, et al.J Endocrinol. 2008 Nov;199(2):221-33. doi: 10.1677/JOE-08-0215. Epub 2008 Aug 20.J Endocrinol. 2008.PMID:18715880
- Obesity hormone leptin: a new target in breast cancer?Surmacz E.Surmacz E.Breast Cancer Res. 2007;9(1):301. doi: 10.1186/bcr1638.Breast Cancer Res. 2007.PMID:17274833Free PMC article.Review.
Cited by
- The tetrad BMI, leptin, leptin/adiponectin (L/A) ratio and CA 15-3 are reliable biomarkers of breast cancer.Santillán-Benítez JG, Mendieta-Zerón H, Gómez-Oliván LM, Torres-Juárez JJ, González-Bañales JM, Hernández-Peña LV, Ordóñez-Quiroz A.Santillán-Benítez JG, et al.J Clin Lab Anal. 2013 Jan;27(1):12-20. doi: 10.1002/jcla.21555. Epub 2013 Jan 4.J Clin Lab Anal. 2013.PMID:23292756Free PMC article.
- Greater Body Fatness Is Associated With Higher Protein Expression of LEPR in Breast Tumor Tissues: A Cross-Sectional Analysis in the Women's Circle of Health Study.Llanos AAM, Aremu JB, Cheng TD, Chen W, Chekmareva MA, Cespedes Feliciano EM, Qin B, Lin Y, Omene C, Khoury T, Hong CC, Yao S, Ambrosone CB, Bandera EV, Demissie K.Llanos AAM, et al.Front Endocrinol (Lausanne). 2022 Jun 29;13:879164. doi: 10.3389/fendo.2022.879164. eCollection 2022.Front Endocrinol (Lausanne). 2022.PMID:35846306Free PMC article.
- O-GlcNAcylation: A New Cancer Hallmark?Fardini Y, Dehennaut V, Lefebvre T, Issad T.Fardini Y, et al.Front Endocrinol (Lausanne). 2013 Aug 12;4:99. doi: 10.3389/fendo.2013.00099. eCollection 2013.Front Endocrinol (Lausanne). 2013.PMID:23964270Free PMC article.
- Concise review: The obesity cancer paradigm: exploration of the interactions and crosstalk with adipose stem cells.Strong AL, Burow ME, Gimble JM, Bunnell BA.Strong AL, et al.Stem Cells. 2015 Feb;33(2):318-26. doi: 10.1002/stem.1857.Stem Cells. 2015.PMID:25267443Free PMC article.Review.
- Relationship between body mass index and incidence of breast cancer.Li HT, Han XH, Liu YX, Leng KM, Dong GM.Li HT, et al.Int J Clin Exp Med. 2015 Jul 15;8(7):11549-53. eCollection 2015.Int J Clin Exp Med. 2015.PMID:26379979Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous